專(zhuān)利名稱(chēng):肺炎鏈球菌菌毛抗原的制作方法
技術(shù)領(lǐng)域:
本發(fā)明涉及多肽,包括來(lái)自肺炎鏈球菌(Sti^ptococcus pneumoniae, S. pneumoniae)的菌毛蛋白質(zhì),包括其片段和變體,及其在肺炎鏈球菌感染的治療和免疫接 種中的使用方法。
背景技術(shù):
革蘭氏陽(yáng)性菌肺炎鏈球菌(也稱(chēng)為Spn或肺炎球菌)是全世界范圍發(fā)病和死 亡的主要原因,與HIV、瘧疾和結(jié)核病一起并稱(chēng)為四大主要的感染性疾病殺手(Bruyn, G. Α. W.禾口 van Furth, R. (1991)Eur. J. Clin. Microbiol. Infect. Dis. 10,897-910 ; Ryan, M. W.禾口 Antonelli,P. J. (2000)Laryngoscope 110,961-964 ;Cutts, F.Τ.,Zaman, S. Μ. , Enwere, G. , Jaffar, S. , Levine, 0. S. , Okoko, C. Oluwalana, Α. , Vaughan, S., Obaro, Α. , Leach, Α.等,(2005) Lancet 365,1139-1 146 ;Swiatlo, Ε. , Champlin, F. R., HoIman, S. C.,Wilson, W. W. &ffatt, J. Μ. (2002) Infect. Immun. 70,412—415 ;Sandgren, Α., Albiger, B. , Orihuela, C. , Tuomanen, Ε. , Normark, S.禾口 Henriques-Normark, B. (2005) J. Infect. Dis. 192,791_800)。肺炎鏈球菌不僅是導(dǎo)致呼吸道感染如中耳炎、鼻竇炎和 社群獲得性肺炎的主要原因,而且是侵入性疾病如敗血癥和腦膜炎中的重要病原體。雖 然肺炎球菌是一種破壞性病原體,但它也大量無(wú)害地定居在日間護(hù)理中心的健康兒童 中(HenriquesNormark, B. , Christensson, B. , Sandgren, Α. , Noreen, B. , Sylvan, S., Burman, L. G.和 Olsson-Liljequist, B. (2003)Microb. Drug Resist. 9,337-344 ;Nunes, S. , Sa-Leao R- ,Carri90, J.,Alves, C. R. , Mato, R. , Ανδ, Α. B. , Saldanha, J. , Almeida, J. S. , Sanches, I. S.和 de Lencastre,H. (2005) J. Clin. Microbiol. 43,1285-1293)。肺炎 球菌疾病的重要毒力因素在于多糖莢膜,肺炎球菌通過(guò)多糖莢膜分成至少90種不同的血 清型(Henrichsen, J. (1995) J. Clin. Microbiol. 33,2759-2762)。已描述了其他對(duì)毒力具 有重要作用的遺傳因子,例如CbpA(膽堿-結(jié)合蛋白A)和肺炎鏈球菌溶血素(Lau,G. W., Haataja, S. ,Lonetto, Μ. ,Kensit,S. Ε. ,Marra,Α. ,Bryant,A. P. ,McDevitt, D. , Morrison, D. Α.禾口 Holden,D. W. (2001)Mol. Microbiol. 40,555-571 ;Rosenow, C. ,Ryan, P. ,Weiser, J. N. , Johnson, S. , Fontan, P. , Ortqvist, Α.禾口 Masure, H. R. (1997)Mol. Microbiol. 25, 819-829 ;Tuomanen, Ε. (1999)Current Opin. Biol. 2,35-39)。肺炎鏈球菌感染可通過(guò)初始在鼻咽部建群而引發(fā)的侵入性疾病,但粘附機(jī)制 尚不清楚。有莢膜肺炎球菌的體外粘附比無(wú)莢膜的無(wú)毒力衍生物要低得多(Swiatlo, Ε. , Champlin, F. R. , HoIman, S. C. , Wilson, W. W. &ffatt, J. Μ. (2002) Infect. Immun. 70, 412-415),但莢膜表達(dá)是在上氣道成功建群的必需因素。這些發(fā)現(xiàn)提示,肺炎球菌在體內(nèi) 即使存在厚莢膜也具有粘附性(Sandgren, A.,Albiger, B.,Orihuela, C.,Tuomanen, E., Normark, S.禾口 Henriques—Normark,B. (2005)J. Infect. Dis. 192,791—800)。在其他革蘭氏陽(yáng)性菌,例如白喉棒狀桿菌(Corynebacteriumdiphtheriae) (Ton-That, H. , Marraffini, L. A.禾口 Schneewind, 0. (2004)Mol.Microbiol.53,251-261 ; Ton-That, H.和 Schneewind, 0. (2003) Mol. Microbiol. 50,1429-1438),放線菌 (Actinomyces, spp. ) (Kelstrup, J.,Theilade, J.禾口 Fejerskov,0. (1979) Scand. J. Dent. Res. 87,415-423)和近來(lái)發(fā)現(xiàn)的A型鏈球菌(GAS)和B型鏈球菌(GBS) (Mora, Μ.,Bensi, G. , Capo, S. , Falugi, F. , Zingaretti, C. , Manetti, Α. G. 0. , Maggi, Τ. , Taddei, Α. R., Grandi, G.和 Telford, J. L. (2005)Proc. Natl. Acad. Sci. USA 102,15641-15646 ;Lauer, P. , Rinaudo, C. D. , Soriani,M. ,Margarit, I. ,Mainone, D. , Rosini, R. , Taddei, A. R. ,Mora, M.,Rappuoli, R.,Grandi, G.和 Telford, J. L. (2005) Science 309,105)中,電鏡鑒定到菌 毛樣表面結(jié)構(gòu)并通過(guò)遺傳以及生物化學(xué)方法進(jìn)行表征(T0n-That,H.,Marraffini,L.A.和 Schneewind,0. (2004)Mol. Microbiol. 53,251-261;Ton_That,H.禾口 Schneewind,0. (2003) Mol. Microbiol. 50,1429-1438 ;Mora, Μ. , Bensi, G. ,Capo,S. ,Falugi,F. ,Zingaretti, C., Manetti, Α. G. 0. ,Maggi,Τ. ,Taddei, Α. R. ,Grandi, G.禾口 Telford,J. L. (2005)Proc. Natl. Acad. Sci. USA 102,15641-15646 ;Lauer, P. , Rinaudo, C. D. , Soriani, Μ. , Margarit, I., Mainone, D. , Rosini, R. , Taddei, Α. R. , Mora, Μ. , Rappuoli, R. , Grandi, G.禾口 Telford, J.L. (2005) Science 309,105)。在放線菌中,1型菌毛基因介導(dǎo)牙齒和粘膜表面粘附(Li, T.,Khah, M. K.,Slavnic, S.,Johansson, I.禾口 StrOmberg, N. (2001) Infect Immun. 69, 7224-7233)。然而,仍然需要關(guān)于致病性鏈球菌的菌毛和其他抗原在感染性疾病中的生理 學(xué)作用和功能的關(guān)系數(shù)據(jù)。
革蘭氏陽(yáng)性菌毛是由轉(zhuǎn)肽酶反應(yīng)形成的延長(zhǎng)的聚合物,所述轉(zhuǎn)肽酶反應(yīng)涉及由特 定的分選酶(sortase)進(jìn)行組裝的含有特定氨基酸基序的亞基蛋白質(zhì)的共價(jià)鍵交聯(lián)。這種 分選酶也與菌毛和肽聚糖細(xì)胞壁的共價(jià)粘附有關(guān)。
發(fā)明內(nèi)容
本發(fā)明描述了來(lái)自肺炎鏈球菌的多肽。在一些方面,本文所述的多肽包括來(lái)自肺 炎鏈球菌的菌毛肽。在其他方面,描述了來(lái)自肺炎鏈球菌的其他多肽。本文所述的肺炎鏈 球菌多肽可用于針對(duì)肺炎鏈球菌感染的治療和免疫接種的方法中。在一些方面,本發(fā)明描述了來(lái)自肺炎鏈球菌INV104B第二菌毛島(菌毛I(xiàn)I島 (INV104B))的菌毛多肽。在其他方面,本發(fā)明描述了在肺炎鏈球菌23F、INV200和0XC141 中鑒定的菌毛多肽。認(rèn)為該菌毛在肺炎鏈球菌的致病過(guò)程中起作用。在其他方面,本發(fā)明描述了由肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的分離的菌 毛。在一些實(shí)施方式中,菌毛包括分選酶。在一些實(shí)施方式中,菌毛包括LPXTG細(xì)胞壁錨定 蛋白,如具有SEQ ID NO :2,4和/或6氨基酸序列的多肽,或其加工形式。在一些實(shí)施方式中,通過(guò)酶消化(例如,用一種或多種酶,如肽聚糖水解酶(如,變 溶菌素、溶葡萄球菌素和溶菌酶))從細(xì)胞分離菌毛。在一些實(shí)施方式中,通過(guò)機(jī)械剪切(例 如,通過(guò)超聲處理)從細(xì)胞分離菌毛。在一些實(shí)施方式中,菌毛基本不含細(xì)菌細(xì)胞。在一些 實(shí)施方式中,本發(fā)明提供了產(chǎn)生菌毛(例如,肺炎鏈球菌菌毛)的方法,所述方法包括使產(chǎn) 生菌毛的細(xì)胞經(jīng)歷酶消化或機(jī)械剪切以及從細(xì)胞分離菌毛。在其他方面,本發(fā)明提供了免疫原性組合物,其包含一種或多種分離的菌毛(例 如肺炎鏈球菌菌毛)。在其他方面,本發(fā)明提供了一種分離的肺炎鏈球菌分選酶,所述分選酶是SEQ IDNO 282, SEQ ID NO :1386,SEQ ID NO 676 或 SEQ ID NO 1123 中的一種。在其他方面,本發(fā)明提供了分離的肺炎鏈球菌LPXTG細(xì)胞壁錨定蛋白,所述LPXTG 細(xì)胞壁錨定蛋白是 SEQ ID NO :2,SEQ ID NO :4,SEQ ID NO :6,SEQ IDNO :7,SEQ ID NO 8 或SEQ ID NO 9中的一種。 在其他方面,本發(fā)明提供了分離肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛的方 法,所述方法包括使產(chǎn)生肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛的細(xì)菌細(xì)胞經(jīng)歷酶消化 (如,變?nèi)芫?或或機(jī)械剪切(如,超聲處理),以及從細(xì)胞分離菌毛。在一些實(shí)施方式中, 分離包括密度梯度離心。在一些實(shí)施方式中,分離包括使用例如凝膠過(guò)濾色譜,根據(jù)大小分 離組分以降低多分散性。在其他方面,本發(fā)明提供了特異性結(jié)合肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌 毛的抗體。在一些實(shí)施方式中,所述抗體是單克隆抗體、多克隆抗體、嵌合抗體、人抗體、人 源化抗體、單鏈抗體或Fab片段。在其他方面,本發(fā)明提供了 一種免疫原性組合物,其包含低聚物形式的純化 的肺炎鏈球菌菌毛I(xiàn)I島(INV104B)多肽。在一些實(shí)施方式中,所述多肽是超寡聚體 (hyperoligomer).在其它實(shí)施方式中,所述多肽是肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼 的LPXTG細(xì)胞壁錨定蛋白的片段。在其他方面,本發(fā)明提供了誘導(dǎo)針對(duì)肺炎鏈球菌的免疫應(yīng)答的方法。在一些實(shí)施 方式中,所述方法包括給予對(duì)象有效量的肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛。在其他方面,本發(fā)明提供了檢測(cè)對(duì)象是否感染肺炎鏈球菌的方法。在一些實(shí)施方 式中,所述方法包括分析來(lái)自對(duì)象的樣品中是否存在肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼 菌毛的抗體。在其他方面,本發(fā)明提供了檢測(cè)對(duì)象是否感染肺炎鏈球菌的方法。在一些實(shí)施方 式中,所述方法包括使樣品與抗體相接觸以及檢測(cè)所述抗體與樣品組分的結(jié)合。在一些實(shí) 施方式中,所述抗體結(jié)合菌毛組分。在其它實(shí)施方式中,所述抗體結(jié)合菌毛復(fù)合物。在其他方面,本發(fā)明提供了治療肺炎鏈球菌感染對(duì)象的方法。在一些實(shí)施方式中, 所述方法包括給予對(duì)象有效量的特異性結(jié)合肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛的 試劑。在一些實(shí)施方式中,所述試劑是抗體。在一些實(shí)施方式中,所述抗體阻斷肺炎鏈球菌 附著于細(xì)胞。在一些實(shí)施方式中,所述抗體特異性結(jié)合肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編 碼的一種或多種LPXTG細(xì)胞壁錨定蛋白。在其他方面,本發(fā)明提供了確定肺炎鏈球菌感染對(duì)象的療程的方法。在一些 實(shí)施方式中,所述方法包括分析來(lái)自對(duì)象的樣品中是否存在針對(duì)肺炎鏈球菌菌毛I(xiàn)I島 (INV104B)編碼菌毛的抗體,以及如果檢測(cè)到存在這種抗體則給予對(duì)象抗炎藥。在其它 實(shí)施方式中,所述方法包括分析來(lái)自對(duì)象的樣品中是否存在針對(duì)肺炎鏈球菌菌毛I(xiàn)I島 (INV104B)編碼菌毛的抗體,以及如果沒(méi)有檢測(cè)到這種抗體則給予對(duì)象抗生素。在其他方面,本發(fā)明提供了分離的菌毛和菌毛樣多聚體,其包含最多具有30個(gè)氨 基酸取代、插入或缺失的肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛蛋白的氨基酸序列。 在一些實(shí)施方式中,該氨基酸序列最多具有20個(gè)氨基酸取代、插入或缺失。在其它實(shí)施方 式中,該氨基酸序列最多具有10個(gè)氨基酸取代、插入或缺失。在其它實(shí)施方式中,該氨基酸 序列最多具有5個(gè)氨基酸取代、插入或缺失。
在其他方面,本發(fā)明提供了具有肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的一種或多 種LPXTG細(xì)胞壁錨定蛋白的氨基酸序列的多肽。在其他方面,本發(fā)明提供了一種或多種肺 炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的一種或多種LPXTG細(xì)胞壁錨定蛋白的免疫原性片段。 在其他方面,本發(fā)明提供了編碼以下多肽的多核苷酸,所述多肽具有肺炎鏈球菌菌毛I(xiàn)I島 (INV104B)編碼的一種或多種LPXTG細(xì)胞壁錨定蛋白的氨基酸序列。在其他方面,本發(fā)明提供了具有氨基酸序列SEQ ID NO :2、4、6、7、8和9的純化的 多肽。在其他方面,本發(fā)明提供了具有SEQ ID N0:2、4、6、7、8和9的10個(gè)連續(xù)殘基的純化 的多肽。在其他方面,本發(fā)明提供了純化的多肽,其具有與SEQ ID N0:2、4、6、7、8和9至少 85%相同的氨基酸序列。
在其他方面,本發(fā)明提供了純化的多肽,其與選自SEQ ID NO 29到SEQ IDNO 1742的序列或其免疫原性片段至少具有85%的序列相同性。在其他方面,本發(fā)明提供了純 化的多肽,其具有選自SEQ ID N0:29到SEQ ID NO 1742的氨基酸序列或其免疫原性片段。在一些實(shí)施方式中,本發(fā)明提供了純化的0CX141多肽,其與選自下組的序列具有 至少85%的序列相同性SEQ ID NO 53,SEQ ID NO :65、SEQ ID NO 70、SEQ ID NO 99、SEQ ID NO 104,SEQ ID NO 117,SEQ ID NO 135、SEQ ID NO 177,SEQ ID NO 178、SEQ ID NO: 198,SEQ ID NO 235,SEQID NO 236、SEQ ID NO :237、SEQ ID NO 242、SEQ ID NO 247、SEQ ID NO 248, SEQ ID NO 250, SEQ ID NO :25USEQ ID NO 252, SEQ ID NO 253, SEQ ID NO: 433,SEQ ID NO 439、SEQ ID NO 444、SEQ ID NO :538、SEQID NO 539、SEQ ID NO 540、SEQ ID NO :54USEQ ID NO 542, SEQ ID NO 543, SEQ ID NO 544, SEQ ID NO 545, SEQ ID NO: 581或SEQ ID N0:593、或其免疫原性片段。在其它實(shí)施方式中,本發(fā)明提供了純化的INV200多肽,其與選自下組的序列具有 至少85%的序列相同性SEQ ID N0:626、SEQ ID NO :628、SEQ ID NO :629、SEQ ID NO :630、 SEQ ID N0:631、SEQ ID NO :632、SEQ ID NO :639、SEQ ID NO :645、SEQ ID NO :747、SEQ ID N0:751、SEQ ID NO :752、SEQID NO :783、SEQ ID NO :786、SEQ ID NO :787、SEQ ID NO :810、 SEQ IDNO :812、SEQ ID N0:813、SEQ ID NO :824、SEQ ID N0:831、SEQ ID NO 842, SEQ ID NO 847,SEQ ID NO :875、SEQ ID NO :876、SEQ ID NO :879、SEQ ID NO :880、SEQ ID NO :882、 SEQ ID N0:913、SEQ ID NO :914、SEQID N0:925、SEQ ID NO :926、SEQ ID NO 947, SEQ ID NO 948,SEQ ID NO :968、SEQ ID NO :987、SEQ ID NO :988、SEQ ID NO :990、SEQ ID NO :992、 SEQ ID N0:1003、SEQ ID N0:1007、SEQ ID N0:1008、SEQ ID N0:1036、SEQ ID N0:1082、 SEQ ID N0:1120、或SEQ ID NO :1123、或其免疫原性片段。在其他實(shí)施方式中,本發(fā)明提供了純化的23F多肽,其與選自下組的序列具有至 少 85% 的序列相同性=SEQ ID NO :1297、SEQ ID NO :1309、SEQ ID NO :1311、SEQ ID NO 1343、SEQ ID N0:1362、SEQ ID N0:1364、SEQ ID N0:1434、SEQ ID N0:1451、SEQ ID NO: 1455,SEQ ID NO 1466,SEQ ID NO 14678,SEQ ID NO 1470,SEQ ID NO : 1474、SEQ ID NO: 1484、SEQ ID N0:1485、SEQ ID N0:1486、SEQ ID N0:1487、或 SEQ ID N0:1491、或其免疫 原性片段。在其他方面,本發(fā)明提供了肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的LPXTG細(xì)胞壁 錨定蛋白的免疫原性片段。在其他方面,本發(fā)明提供了具有多核苷酸序列SEQ ID NO :1、3和5的分離的核酸。在其他方面,本發(fā)明提供了分離的核酸,其在嚴(yán)謹(jǐn)條件下與雜交探針雜交,其中所述探針具 有多核苷酸序列SEQ ID NO :1、3和5或SEQ ID NO :1、3和5的互補(bǔ)序列。在其他方面,本 發(fā)明提供了分離的核酸,其具有編碼與SEQ IDNO :2、4、6、7、8和9至少85%相同的氨基酸 序列的序列。在其他方面,本發(fā)明提供了分離的核酸,其具有編碼與選自SEQ ID N0:29到SEQ ID NO 1742的序列至少85%相同的氨基酸序列的序列。在其他方面,本發(fā)明提供了分離的 核酸,其具有編碼選自SEQ ID NO 29到SEQ ID NO 1742的氨基酸序列的序列。
在其他方面,本發(fā)明提供了誘導(dǎo)針對(duì)肺炎鏈球菌的免疫應(yīng)答的方法。在一些實(shí)施 方式中,所述方法包括給予對(duì)象有效量的肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的LPXTG細(xì) 胞壁錨定蛋白的免疫原性片段。在一些實(shí)施方式中,所述對(duì)象是人。在其他方面,本發(fā)明提供了針對(duì)細(xì)胞中肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌 毛蛋白的抗體。在一些實(shí)施方式中,所述方法包括在細(xì)胞中表達(dá)編碼肺炎鏈球菌菌毛I(xiàn)I島 (INV104B)編碼菌毛蛋白的抗體的核酸。在一些實(shí)施方式中,所述菌毛蛋白是LPXTG細(xì)胞壁 錨定蛋白。在其他方面,本發(fā)明提供了從包含肺炎鏈球菌的樣品純化肺炎鏈球菌的方法。所 述方法包括提供抗體結(jié)合于固相載體的親和基質(zhì);使所述樣品與該親和基質(zhì)接觸以形成 親和基質(zhì)-肺炎鏈球菌復(fù)合物;使該親和基質(zhì)_肺炎鏈球菌復(fù)合物與樣品其余部分分離; 和由該親和基質(zhì)釋放肺炎鏈球菌。在其他方面,本發(fā)明提供了將細(xì)胞毒劑或診斷試劑遞送至肺炎鏈球菌的方法。所 述方法包括提供偶聯(lián)于抗體或其片段的細(xì)胞毒劑或診斷試劑;和使肺炎鏈球菌接觸所述 抗體_試劑或片段_試劑偶聯(lián)物。在其他方面,本發(fā)明提供了鑒定肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛的結(jié) 合調(diào)節(jié)劑的方法。所述方法包括使肺炎鏈球菌菌毛易于結(jié)合的動(dòng)物細(xì)胞與候選化合物和 具有肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛的細(xì)菌細(xì)胞相接觸;以及測(cè)定細(xì)菌細(xì)胞與 動(dòng)物細(xì)胞的結(jié)合是否受到抑制。在一些實(shí)施方式中,結(jié)合活性的抑制預(yù)示該化合物是肺炎 鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛的結(jié)合抑制劑。在其他方面,本發(fā)明提供了鑒定肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛活 性的結(jié)合調(diào)節(jié)劑的方法。所述方法包括使肺炎鏈球菌菌毛易于結(jié)合的細(xì)胞與候選化合 物和肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛相接觸;以及測(cè)定菌毛與細(xì)胞的結(jié)合是 否受到抑制。在一些實(shí)施方式中,結(jié)合活性的抑制預(yù)示該化合物是肺炎鏈球菌菌毛I(xiàn)I島 (INV104B)編碼的菌毛的結(jié)合抑制劑。在其他方面,本發(fā)明提供了鑒定肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛的結(jié) 合調(diào)節(jié)劑的方法。所述方法包括使肺炎鏈球菌菌毛易于結(jié)合的細(xì)胞與候選化合物和肺炎 鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛蛋白或其細(xì)胞結(jié)合片段相接觸;以及測(cè)定菌毛蛋白 或其細(xì)胞結(jié)合片段與細(xì)胞的結(jié)合是否受到抑制。在一些實(shí)施方式中,結(jié)合活性的抑制預(yù)示 該化合物是肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛的結(jié)合抑制劑。在其他方面,本發(fā)明提供了分離肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛的方 法。所述方法包括使產(chǎn)生肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛的肺炎鏈球菌細(xì)胞 接受超聲處理或分解酶消化;密度梯度離心分離非細(xì)胞組分;和分離肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛。在一些實(shí)施方式中,所述分解酶是變?nèi)芫?。在其它?shí)施方式中, 產(chǎn)生肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛的肺炎鏈球菌細(xì)胞是肺炎鏈球菌TIGR4 細(xì)胞。除非另外定義,本文中所使用的所有技術(shù)和科學(xué)術(shù)語(yǔ)具有本領(lǐng)域普通技術(shù)人員通 常所理解的含義。雖然在本發(fā)明的實(shí)施或測(cè)試中可以采用類(lèi)似于或等同于本文所述的那些 方法和材料,但是,下面描述了合適的方法和材料。在出現(xiàn)矛盾的情況下,以本說(shuō)明書(shū)的定 義為準(zhǔn)。此外,材料、方法和實(shí)施例都只是說(shuō)明性的,并不構(gòu)成限制。在附圖和下述描述中詳細(xì)描述了本發(fā)明的一種或多種實(shí)施方式。通過(guò)以下說(shuō)明書(shū) 和附圖以及附加的實(shí)施方式,本發(fā)明的其他特征、目的和優(yōu)點(diǎn)將是顯而易見(jiàn)的。附圖簡(jiǎn)要說(shuō)明
圖1是肺炎鏈球菌菌毛I(xiàn)I島(INV104B)的示意圖。發(fā)明詳述申請(qǐng)人:鑒定了來(lái)自肺炎鏈球菌(也稱(chēng)為肺炎球菌)的新的多肽序列,包括 新的菌毛多肽和其他可用作抗原的多肽。在由基因研究機(jī)構(gòu)(The Institute for GenomicResearch)(參見(jiàn)網(wǎng)站“tigr. org”)測(cè)序的肺炎鏈球菌分離物INV104的未完成基因 組序列中鑒定到新的菌毛多肽序列。這些菌毛多肽序列由本文中稱(chēng)為菌毛I(xiàn)I島(INV104B) 的致病性島編碼,它出現(xiàn)在一些但并非全部臨床肺炎球菌分離物中。菌毛對(duì)于肺炎球菌附 著于肺上皮細(xì)胞以及建群是重要的。此外,還分析了肺炎鏈球菌菌株23F、INV200和0XC141 的 Sanger 不完全基因組(參見(jiàn)網(wǎng)站“sanger. ac. uk/Projects/Microbes/”)以鑒定 INV104 中不存在的多肽的編碼基因,其結(jié)果包括額外的菌毛多肽以及大量其他非-INV104多肽。 因此,本發(fā)明提供了肺炎鏈球菌纖毛、菌毛和其他多肽組合物以及所述物質(zhì)在治療、診斷、 免疫接種對(duì)抗肺炎鏈球菌感染中的應(yīng)用。本文所用術(shù)語(yǔ)“肺炎鏈球菌多肽”表示包括肺炎 鏈球菌菌毛I(xiàn)I島(INV104B)菌毛多肽,來(lái)自23F、INV200和0XC141的菌毛多肽以及其他來(lái) 自肺炎鏈球菌的多肽。并且,本文所用術(shù)語(yǔ)“肺炎鏈球菌菌毛多肽”表示肺炎鏈球菌菌毛I(xiàn)I 島(INV104B)菌毛多肽以及來(lái)自23F、INV200和0XC141的菌毛多肽。INV104B菌毛I(xiàn)I島的肺炎鏈球菌菌毛本文描述了對(duì)應(yīng)于菌株TIGR4的肺炎鏈球菌分離物INV104B (ST227,血清型1)的 sp 1008和sp 1009的基因之間6. 5kb插入物編碼的肺炎球菌菌毛(如圖1所示)。肺炎鏈 球菌分離物INV104B的這個(gè)區(qū)域在這里稱(chēng)為“肺炎鏈球菌菌毛I(xiàn)I島(INV104B) ”。肺炎鏈球 菌菌毛I(xiàn)I島(INV104B)編碼三種LPXTG細(xì)胞壁錨定蛋白(在這里稱(chēng)為L(zhǎng)PXTG-I、LPXTG-IA 禾口 LPXTG-2)、LepA肽酶(orf01289 ;SEQ IDNO 673)和兩種預(yù)測(cè)的分選酶(在這里稱(chēng)為分 選-1(SEQ ID NO 676)和分選_2(SEQID NO: 1123))。這些LepA和分選酶序列參見(jiàn)實(shí)施例 4。這里提供了 LPXTG-I (orf01290-長(zhǎng))的示例性核酸序列ATGAACGTTCAATATGATTTTAAGAAGATTCAATATTTTACCAGTAGTTTAGTTATCTTTCTCGCTATT CTTTTTTTGTGTGCACCAATTAATTCTTTACGTGCAGATTCAATAACTGAACCTCAGACAACTCTGCACAAAACGAT TACTCCGATATCAGGGCAAAAAGACCAGTATGAGTTGTCACTGGATATCACATCTAAACTGGGAACGGAGACCCAGT CAGAACCCTTGGATGTAGTCTTGGTTGCCGATCTTTCAGGGAGTATGGAAGAGCGAGATGTGTGGTCTTACTCTAGT AGACGATACATTAGTAGGATTGAAGCACTAAAACATACACTGAAAGGTGTGAATGGTCGTCAGGGGCTCATTGATACAATTCTTTCTAATTCCCAAAACCGTCTGTCTATAGTTGGTTTTGCCGGAAAGATTGATAATCAGTATAATGACCGTT ATTATAATGAATATTATCTGAGTTATCAATATGGAACTTGGCCAAATTGAGCTGGTTGGTATTCAAATATCTCTTCA TATGATGATGCTAAAACTTTAGTATCTTGGAGCACGGATTCTAATAGCTCAAAAAATATTGTTAGTTCGTTAACAAT TGCTGACTCTAGTCGTTCTTATGGTATGGACGCGGGCATTGGCACTGGGACAAATATAAATGCTGGGTTAACTGAAG CTCAAAGATTGTTGCAAAGTGCAAGGGCTGGGGCAAAAAAAGTAGTTATTCTGCTGTCAGATGGCGAAGCTAATATG TATTACGAGTCTAATAGTGGGAGAACAATATATAACTATTATTCTAATCCAAATGTGGGACGTATGATTGATACTCC ATATTGGTTTACCTCTGGTTTAGAGAGAGGAATGCTGAATATATCTAGTTTAATAGCTCCAAAAATAGATGGCTTTT ATTCAATCAAATTCAGATATATAGGTTCAAACGATAGTATCACATCTCTTAAAGGATATATCAGTGGTTATAATTCT GGAATCCCCAACGAAATATTTTCTGCCAATAATGAAAATGACTTGCAACAAAAATTCAAAGAAATCACAGATAAAAT TCTACCTCTAGGCGTACACCATGTAACTATATCAGATGTCTTGTCCAAGTACGTGCAGCTGTTACCTGGTGATGCTT CACACCTTCGTGTCGTCAAAATCAAGGATGGTAACGAGCAAGAACTGAATGACAATCAAGTTACGATTGAAACTAAG AAGAACGAACAGGGATTAGTGGAAGTAACAGCCAAGTTTAATCCGAGTTACACTTTGGAGGATGACGCCAAGTACGT TCTCAAGTTTACTGTCACCTCTAGCCAAGAGGCATTTGATGCGATTGCGGGTGATAAGACACTTACTAGTGATGATG CCGAAGAAGCCGATGCTACTAAACTCTACTCCAACAAGGGGGCAAAAGTTGCCTATTCCTATGGTATTGGGACCTCA CGTACCAAAATAAAAGACTATTCTGAGAAGCCCACTTTCAAGCCGTCAGATCCATTGACGGTTCCTGTAGAGATTGA GTGGAAAGGTGTGGATGGAAAATCAAATCCATCAGCAAATCGTCCACCTAGTGTCGAATTAAACTTAAACCAAAAGA AAGATGGAAGTATAAAGGATTCCTATCGAAAGGTCACTAGTCCAGTTCAAACGAATAGTTTTACTGAAAATACTAGT TTTGCAAAGGTAGCTAAGGGATATGACTACGAACTGAAAGCACCAGACGCTCCGGGATACACAGTCGAAGTTCAAAA GACAGGTACGAAAGAGAAACCATCCTTCAAAGTTATTTACCGACAGCTTCCAAGTCTCACCGTAAAGAAAATCCTAG AAGGTGAACAATCACCTAATAAATCTTTCACAATTAATGTTACCTTTTCAGATAAGGATGGCAAGCCGATTAACGGC AAGTTTGGGAATACAACAGTGACTAACGGGAAAGCACAGATTTCTCTCAAAAATAGTCAGGAAACTGCCCTCAGTTA TCTGCCTCGTGATACCCACTATAAGGTGGAAGAAGTAGAGAACTCTAGAACGGGATATCATGTCACCTATGAAAAAC AAGAGGGGACTTTGTCAGAGGATGTTCAAACAATCGTCACCAACCACAGACTTCCGACACTTTCAGTCACAAAAAAA GTTACAGGTGCTTTTGCTAATCTTCTGCAATCCTTTAAGATTACCATTAACGTAAAGGATGCGCAAAATAAACCATT GAATGGATCGTATAGTGCAATAGTAAATAATCAAAAAACAACGCTACAATTCACCAATGGTAAGGCGACAGTTGATC TAAAGAAAGATAAAACCATCAAGATTCTCGACCTTCCTCTAAATGCTCGTTATAGTATCGAAGAAGAAGCAAGTTCG TCTCGTGGGTATCAGGTGTCCTATGATAAAAAAGAAGGAACTCTTGATGCAAATAAGTCTGCGACAGTCACGAATAA TAAAAACAGCGTACCTGAAACGGGAATTGACTTCTTGAGTAGCACTCTCGTGCTTGGAGTCGTTCTTCCTCTAGGAG GGATCTTCTTTATCATCTTACTTGGTCACCTTGTGGTGAATAGGAGGAA(SEQ ID NO 1)這里提供了 LPXTG-I的示例性氨基酸序列MNVQYDFKKIQYFTSSLVIFLAILFLCAPINSLRADSITEPQTTLHKTITPISGQKDQYELSLDITSK LGTETQSEPLDVVLVADLSGSMEERDVWSYSSRRYISRIEALKHTLKGVNGRQGLIDTILSNSQNRLSIVGFAGKI DNQYNDRYYNEYYLSYQYGTffPN 女 AGWYSNISSYDDAKTLVSWSTDSNSSKNIVSSLTIADSSRSYGMDAGIGTG TNINAGLTEAQRLLQSARAGAKKWILLSDGEA匪YYESNSGRTIYNYYSNPNVGRMIDTPYWFTSGLERGMLNISS LIAPKIDGFYSIKFRYIGSNDSITSLKGYISGYNSGIPNEIFSANNENDLQQKFKEITDKILPLGVHHVTISDVLSK YVQLLP⑶ASHLRVVKIKDGNEQELNDNQVTIETKKNEQGLVEVTAKFNPSYTLEDDAKYVLKFTVTSSQEAFDAIA GDKTLTSDDAEEADATKLYSNKGAKVAYSYGIGTSRTKIKDYSEKPTFKPSDPLTVPVEIEWKGVDGKSNPSANRPP SVELNLNQKKDGSIKDSYRKVTSPVQTNSFTENTSFAKVAKGYDYELKAPDAPGYTVEVQKTGTKEKPSFKVIYRQL PSLTVKKILEGEQSPNKSFTINVTFSDKDGKPINGKFGNTTVTNGKAQISLKNSQETALSYLPRDTHYKVEEVENSRTGYHVTYEKQEGTLSEDVQTIVTNHRLPTLSVTKKVTGAFANLLQSFKITINVKDAQNKPLNGSYSAIVNNQKTTLQ FTNGKATVDLKKDKTIKILDLPLNARYSIEEEASSSRGYQVSYDKKEGTLDANKSATVTNNKNSVPETGIDFLSSTL VLGVVLPLGGIFFIILLGHLVVNRRK(SEQ ID NO :769 禾口 2)LPXTG-I包含分選酶底物基序VPXTG (SEQ ID NO 16),如上述SEQ IDNO 2中下劃 線所示。orf01290-長(zhǎng)的序列(SEQ ID NO 1)具有中間終止密碼子,在SEQ ID N0:1中以 粗體下劃線表示。在該終止密碼子處終止的示例性核酸序列(orf01290-短)具有以下轉(zhuǎn) 錄基因序列(LPXTG-IA)ATGGACGCGGGCATTGGCACTGGGACAAATATAAATGCTGGGTTAACTGAAGCTCAAAGATTGTTGCAA AGTGCAAGGGCTGGGGCAAAAAAAGTAGTTATTCTGCTGTCAGATGGCGAAGCTAATATGTATTACGAGTCTAATAG TGGGAGAACAATATATAACTATTATTCTAATCCAAATGTGGGACGTATGATTGATACTCCATATTGGTTTACCTCTG GTTTAGAGAGAGGAATGCTGAATATATCTAGTTTAATAGCTCCAAAAATAGATGGCTTTTATTCAATCAAATTCAGA TATATAGGTTCAAACGATAGTATCACATCTCTTAAAGGATATATCAGTGGTTATAATTCTGGAATCCCCAACGAAAT ATTTTCTGCCAATAATGAAAATGACTTGCAACAAAAATTCAAAGAAATCACAGATAAAATTCTACCTCTAGGCGTAC ACCATGTAACTATATCAGATGTCTTGTCCAAGTACGTGCAGCTGTTACCTGGTGATGCTTCACACCTTCGTGTCGTC AAAATCAAGGATGGTAACGAGCAAGAACTGAATGACAATCAAGTTACGATTGAAACTAAGAAGAACGAACAGGGATT AGTGGAAGTAACAGCCAAGTTTAATCCGAGTTACACTTTGGAGGATGACGCCAAGTACGTTCTCAAGTTTACTGTCA CCTCTAGCCAAGAGGCATTTGATGCGATTGCGGGTGATAAGACACTTACTAGTGATGATGCCGAAGAAGCCGATGCT ACTAAACTCTACTCCAACAAGGGGGCAAAAGTTGCCTATTCCTATGGTATTGGGACCTCACGTACCAAAATAAAAGA CTATTCTGAGAAGCCCACTTTCAAGCCGTCAGATCCATTGACGGTTCCTGTAGAGATTGAGTGGAAAGGTGTGGATG GAAAATCAAATCCATCAGCAAATCGTCCACCTAGTGTCGAATTAAACTTAAACCAAAAGAAAGATGGAAGTATAAAG GATTCCTATCGAAAGGTCACTAGTCCAGTTCAAACGAATAGTTTTACTGAAAATACTAGTTTTGCAAAGGTAGCTAA GGGATATGACTACGAACTGAAAGCACCAGACGCTCCGGGATACACAGTCGAAGTTCAAAAGACAGGTACGAAAGAGA AACCATCCTTCAAAGTTATTTACCGACAGCTTCCAAGTCTCACCGTAAAGAAAATCCTAGAAGGTGAACAATCACCT AATAAATCTTTCACAATTAATGTTACCTTTTCAGATAAGGATGGCAAGCCGATTAACGGCAAGTTTGGGAATACAAC AGTGACTAACGGGAAAGCACAGATTTCTCTCAAAAATAGTCAGGAAACTGCCCTCAGTTATCTGCCTCGTGATACCC ACTATAAGGTGGAAGAAGTAGAGAACTCTAGAACGGGATATCATGTCACCTATGAAAAACAAGAGGGGACTTTGTCA GAGGATGTTCAAACAATCGTCACCAACCACAGACTTCCGACACTTTCAGTCACAAAAAAAGTTACAGGTGCTTTTGC TAATCTTCTGCAATCCTTTAAGATTACCATTAACGTAAAGGATGCGCAAAATAAACCATTGAATGGATCGTATAGTG CAATAGTAAATAATCAAAAAACAACGCTACAATTCACCAATGGTAAGGCGACAGTTGATCTAAAGAAAGATAAAACC ATCAAGATTCTCGACCTTCCTCTAAATGCTCGTTATAGTATCGAAGAAGAAGCAAGTTCGTCTCGTGGGTATCAGGT GTCCTATGATAAAAAAGAAGGAACTCTTGATGCAAATAAGTCTGCGACAGTCACGAATAATAAAAACAGCGTACCTG AAACGGGAATTGACTTCTTGAGTAGCACTCTCGTGCTTGGAGTCGTTCTTCCTCTAGGAGGGATCTTCTTTATCATC TTACTTGGTCACCTTGTGGTGAATAGGAGGAA(SEQ ID NO 3)下面提供了 LPXTG-IA (來(lái)自orf01290-短)的示例性氨基酸序列MDAGIGTGTNINAGLTEAQRLLQSARAGAKKVVILLSDGEA匪YYESNSGRTIYNYYSNPNVGRMIDTP YWFTSGLERGMLNISSLIAPKIDGFYSIKFRYIGSNDSITSLKGYISGYNSGIPNEIFSANNENDLQQKFKEITDKI LPLGVHHVTISDVLSKYVQLLP⑶ASHLRWKIKDGNEQELNDNQVTIETKKNEQGLVEVTAKFNPSYTLEDDAKYV LKFTVTSSQEAFDAIA⑶KTLTSDDAEEADATKLYSNKGAKVAYSYGIGTSRTKIKDYSEKPTFKPSDPLTVPVEIEWKGVDGKSNPSANRPPSVELNLNQKKDGSIKDSYRKVTSPVQTNSFTENTSFAKVAKGYDYELKAPDAPGYTVEVQK TGTKEKPSFKVIYRQLPSLTVKKILEGEQSPNKSFTINVTFSDKDGKPINGKFGNTTVTNGKAQISLKNSQETALSY LPRDTHYKVEEVENSRTGYHVTYEKQEGTLSEDVQTIVTNHRLPTLSVTKKVTGAFANLLQSFKITINVKDAQNKPL NGSYSAIVNNQKTTLQFTNGKATVDLKKDKTIKILDLPLNARYSIEEEASSSRGYQVSYDKKEGTLDANKSAT VTNN KNSVPETGIDFLSSTLVLGVVLPLGGIFFIILLGHLVVNRRK(SEQ ID NO 4)LPXTG-IA包含分選酶底物基序VPXTG (SEQ ID NO 16),如上文SEQ IDNO :4中下劃 線所示。下面提供了 LPXTG-2(orf01287)的示例性核酸序列TTGATGATCATAATGAAAAAAGAAAATAAAAAAACAAAAGAAATAATCATGAAAAAAACATTCTTTAAA AAGCTATTCACTGCAAGCATTGCAGCTATAACCGCTTTGTCCGTATTCAGAGGTGTCCCGACTTTTGCGGATGATAA TTCAGCAATAACCAAAGCAAATGGTGAAAATAATGCTGTTGTGAAGATTAATAAAACGTTGAATATTGCAGAGGGAA TAACAACACCAACAGCGACATTTACATTTAAGTTTACAGAAAAAACAGGACAATCTTCTAACGGTGCGCCATATCAA ACCGGAGTTGCAATTCCAGATAGAAATGTAGAATACAATAAAAATGATCACCCAACTGCTGATAAGATTCAAAAAGC AACAGAAGACATTTTTTCGGGAGTTGCTTATGGCCATGCTGGTGAATACGTTTATGATGTAGCGGAAGCAAAAACTG GATGGCAGGCGATTACCAAAAATGGTAAAACAATTGATGCCATGAGATACGACAAACGTACATATGAAATGCACGTT ATTGTTAAGAATAAAGTAAATGGTGGTGTCTATATTTCATCAGTATACTTTAAGGAAAATAATAAATCTAACGCCCC TAAAGTAGAACCAAGTGAACAAGGCGTTTATAATTTATTTGATAACACATATACCAAAGACGCAAGTAAGGAGCCTA ATCCTGATGATCCGAGTCAAGTAGACCCCAATGCGAAAGCATTAACAATTACTAAAAAAGTTGATGGAGCTTCAGGG GATAAAACAAGAGATTTCCAATTCCATATCAAGATTCAACTTCCAAGTACAAATAAAACAGCAGAAACCCCTGTTAC GAATATTATAGTAAAACATGGATCTAAGTCAGAGGTGTTGGCAGTAGTGACCCCAGCAGATACAGTTGAGTACAATT TTACTCTTAAAGATGGTGAAACATTTACAGTTGAACAACTACCAGCAGGTTCTAAATATACAGTAACTGAAACTGGA GTAGCAGGTTATACAGATTCATCAATTTATACTACAAATGGTGCAGAACAAACATCTCAAGGACAAAAAAATGTAGA TTTTACATTAACAGATATCCTCATAGGTGAAAAGAAAAACGACAACAAAGTTACTAACAAAATCGACGACGTTACTC CTACTGGTCTCTTGATTGATAACCTTCCATTCATTTTGATGATTGGTCTTGGTTTGGCTGGATTTGTTGTCTTGTCT AAAAAACGTAGAGAAGCCTA(SEQ ID NO 5)下面提供了 LPXTG-2的示例性氨基酸序列MIIMKKENKKTKEIIMKKTFFKKLFTASIAAITALSVFRGVPTFADDNSAITKANGENNAVVKINKTLN IAEGITTPTATFTFKFTEKTGQSSNGAPYQTGVAIPDRNVEYNKNDHPTADKIQKATEDIFSGVAYGHAGEYVYDVA EAKTGWQAITKNGKTIDAMRYDKRTYEMHVIVKNKVNGGVYISSVYFKENNKSNAPKVEPSEQGVYNLFDNTYTKDA SKEPNPDDPSQVDPNAKALTITKKVDGASGDKTRDFQFHIKIQLPSTNKTAETPVTNIIVKHGSKSEVLAVVTPADT VEYNFTLKDGETFTVEQLPAGSKYTVTETGVAGYTDSSIYTTNGAEQTSQGQKNVDFTLTDILIGEKKNDNKVTNKI DDVTPTGLLIDNLPFILMIGLGLAGFVVLSKKRREA(SEQ ID NO 6)LPXTG-2包含分選酶底物基序VTXTG (SEQ ID NO 21),如上文SEQ IDNO 6中下劃 線所示。在23F、INV200和0XC141肺炎鏈球菌菌株中鑒定的多肽序列肺炎鏈球菌菌株23F、INV200和0XC141的Sanger不完全基因組不包含肺炎鏈球 菌菌毛I(xiàn)I島(INV104B)區(qū)域。然而,23F、INV200和0XC141編碼分選酶和LPXTG細(xì)胞壁錨 定蛋白,如本文所述。例如,23F和0XC141各自編碼至少一種非肺炎鏈球菌菌株INV104B編 碼的分選酶(分選 _23F(orf01917 ;SEQ IDNO 1386)和分選-0XC141 (orf01672 ;SEQ ID NO:282)),INV200編碼至少三種非肺炎鏈球菌菌株INV104B編碼的細(xì)胞壁錨定蛋白(錨定_1、錨定_2和錨定_3)。下面提供了錨定-l(INV200-orf00426)的示例性氨基酸序列MRVSSDTNIYEYRALSPQQKAALEMIRADLYKFTVPYENLEYRFYKPDWVFGLGYQALATVRWKIEPAT ITVTKKWENVKEGAKKPDVWIQLLKDGKPEGERKRIESDKGQTTFEIPNKDEINKYSVKEVDKEGRDWKHKDFTAGQ PVNKGNGHFEITNTKKEKPKIKVTFKKIAGDTNKDLAGAHLVLKKIFDDGNGLLIKQWDTIGQPVDIDLDAGSYTLT EEKAPDGYMLAAPVSFYVEEDGQIILPKGEDLEAQNDKTITMVDEKIKEKPTKPSGKLATTVEVDGTKADAQKELEL SVATDKVTKTVKDTVVYENLLAGETYKLTGQLMKITADKEEEVATKETTFVADASGNGTTSLEFEDVSLEAGVKYVV YETAESEKEIDFKEGKEKHKVEHKDKDDKAQTVVVTKEKPTKPSGKLATTVEVDGTKADAQKELELSVATDKVTKTV KDTVVYENLLAGETYKLTGQLMKITADKEEEVATKETTFVADASGNGTTSLEFEDVSLEAGVKYVVYETAESEKEID FKEGKEKHKVEHKDKDDKAQTVVVSKIKPEPGAQEVHFSKVNVGGEEIAGAEIHIKQGDTVVASWVSEAGKTHTLKL KPGHYIFHEAVAPGGYLAVTDIHFSVDETGQVTVTDVNGNTAVAEGNKLTVTDQTKPVTPPSPEEPGAQEVHFSKVN VGGEEIAGAEIHIKQ⑶TWASWVSEAGKTHTLKLKPGHYIFHEAVAPGGYLAVTDIHFSVDETGQVTVTDVNGNTA VAEGNKLTVTDQTKPVTPPSPEEPGAQEVHFSKVNVGGEEIAGAEIHIKQ⑶TVVASWVSEAGKTHTLKLKPGHYIF HEAVAPGGYLAVTDIHFSVDETGQVTVTDVNGNTAVAEGNKLTVTDQSADKDKQDKLPNTGETTGTYLSILGMITAV FASLLYRSKKK(SEQ ID NO 7)錨定-1包含分選酶底物基序LPNTG (SEQ ID NO 10),如上文SEQ ID NO 7中下劃 線所示。下面提供了錨定-2(INV200-orf00441)的示例性氨基酸序列MNKGLFEKRCKYSIRKFSLGVASVMIGAAFFGTSPVLADSVQSGSTANLPADLATALATAKENDGRDFE APKVGEDQGSPEVTDGPKTEEELLALEKEKPAEEKPKEDKPAAAKPETPKTVTPEWQTVEKKEQKGTVTIREEKGVR YNQLSSTAQNDNAGKPALFEKKGLTVVANGNATVDLTFKDDSEKGKSRFGVFLKFKDTNNNVFVGYDKDGWFWEYKS PTTSTWYRGSRVAAPETGSTNRLSITLKSDGQLNASNNDVNLFDTVTLPAAVNDHLKNEKKILLKAGSYGNDRTVVS VKTDNQEGVKADDTPAQKETGPVVDDSKVTYDTIQSKVLKAVIDQAFPRVKEYSLNGHTLPGQVQQFNQVFINNHRI TPEVTYKKINETTAEYLMKIRDDAHLINAEMTVRLQVVDNQLHFDVTKIVNHNQVTPGQKIDDERKLLSSISFLGNA LVSVSSDQTGAKFDGATMSNNTHVS⑶DHIDVTNPMKDLAKGYMYGFVSTDKLAAGVWSNSQNSYGGGSNDWTRLTA YKETVGNANYVGIHSSEffQffEKAYKGIVFPEYTKELPSAKVVITEDANADKKVDWQDGAIAYRSIMNNPQGWEKVKD ITAYRIAMNFGSQAQNPFLMTLDGIKKINLHTDGLGQGVLLKGYGSEGHDSGHLNYADIGKRIGGVEDFKTLIEKAK KYGAHLGIHVNASETYPESKYFNEKILRKNPDGSYSYGWNWLDQGINIDAAYDLAHGRLARWEDLKKKLGDGLDFIY VDVWGNGQS⑶NGAWATHVLAKEINKQGWRFAIEWGHGGEYDSTFHHWAADLTYGGYTNKGINSAITRFIRNHQKDA WVGDYRSYGGAANYPLLGGYSMKDFEGWQGRSDYNGYVTNLFAHDVMTKYFQHFTVSKWENGTPVTMTDNGSTYKffT PEMRVELVDADNNKVVVTRKSNDVNSPQYRERTVTLNGRVIQDGSAYLTPWNWDANGKKLSTDKEKMYYFNTQAGAT TWTLPSDWAKSKVYLYKLTDQGKTEEQELTVKDGKITLDLLANQPYVLYRSKQTNPEMSWSEGMHIYDQGFNSGTLK HWTISGDASKAEIVKSQGANDMLRIQGNKEKVSLTQKLTGLKPNTKYAVYVGVDNRSNAKASITVNTGEKEVTTYTN KSLALNYVKAYAHNTRRDNATVDDTSYFQNMYAFFTTGADVSNVTLTLSREA⑶QATYFDEIRTFENNSSMYGDKHD TGKGTFKQDFENVAQGIFPFVVGGVEGVEDNRTHLSEKHNPYTQRGWNGKKVDDVIEGNWSLKTNGLVSRRNLVYQT IPQNFRFEAGKTYRVTFEYEAGSDNTYAFVVGKGEFQSGRRGTQASNLEMHELPNTWTDSKKAKKATFLVTGAETGD TWVGIYSTGNASNTRGDSGGNANFRGYNDFMMDNLQIEEITLTGKMLTENALKNYLPTVAMTNYTKESMDALKEAVF NLSQADDDISVEEARAEIAKIEALKNALVQKKTALVADDFASLTAPAQAQEGLANAFDGNVSSLWHTSWNGGDVGKPATMVLKEPTEITGLRYVPRGSGSNGNLRDVKLVVTDESGKEHTFTATDWPDNNKPKDIDFGKTIKAKKIVLTGTKTY GDG⑶KYQSAAELIFTRPQVAETPLDLSGYEAALAKAQKLTDKDNQEEVASVQASMKYATDNHLLTERMVEYFADYL NQLKDSATKPDAPTVEKPEFKLSSLVSEQGKTPDYKQEIARPETPEQILPATGESQSDTSLFLASVSLALSALFVVK TKKD(SEQ ID NO 8)錨定-2包含分選酶底物基序LPATG (SEQ ID NO 10),如上文SEQ ID NO 8中下劃 線所示。下面提供了錨定-3(INV200-orf03448)的示例性氨基酸序列MRVSSDTNIYEYRALSPQQKAALEMIRADLYKFTVPYENLEYRFYKPDWVFGLGYQALATVRWKIEPAT ITVTKKWENVKEGAKKPDVWIQLLKDGKPEGERKRIESDKGQTTFEIPNKDEINKYSVKEVDKEGRDWKHKDFTAGQ PVNKGNGHFEITNTKKEKPKIKVTFKKIAGDTNKDLAGAHLVLKKIFDDGNGLLIKQWDTIGQPVDIDLDAGSYTLT EEKAPDGYMLAAPVSFYVEEDGQIILPKGEDLEAQNDKTITMVDEKIKEKPTKPSGKLATTVEVDGTKADAQKELEL SVATDKVTKTVKDTVVYENLLAGETYKLTGQLMKITADKEEEVATKETTFVADASGNGTTSLEFEDVSLEA GVKYVV YETAESEKEIDFKEGKEKHKVEHKDKDDKAQTVVVTKEKPTKPSGKLATTVEVDGTKADAQKELELSVATDKVTKTV KDTVVYENLLAGETYKLTGQLMKITADKEEEVATKETTFVADASGNGTTSLEFEDVSLEAGVKYVVYETAESEKEID FKEGKEKHKVEHKDKDDKAQTVVVTKEKPTKPSGKLATTVEVDGTKADAQKELELSVATDKVTKTVKDTVVYENLLA GETYKLTGQLMKITADKEEEVATKETTFVADASGNGTTSLEFEDVSLEAGVKYVVYETAESEKEIDFKEGKEKHKVE HKDKDDKAQTVVVTKEKPTKPSGKLATTVEVDGTKADAQKELELSVATDKVTKTVKDTVVYENLLAGETYKLTGQLM KITADKEEEVATKETTFVADASGNGTTSLEFEDVSLEAGVKYVVYETAESEKEIDFKEGKEKHKVEHKDKDDKAQTV VV SKIKPEPGAQEVHFSKVNVGGEEIAGAEI HI KQiiDTWASWVSEAGKTHTLKLKPGHY IFHEAVAPGGYLAVTDI HFSVDETGQVTVTDVNGNTAVAEGNKLTVTDQTKPVTPPSPEEPGAQEVHFSKVNVGGEEIAGAEIHIKQ⑶TVVAS WVSEAGKTHTLKLKPGHYIFHEAVAPGGYLAVTDIHFSVDETGQVTVTDVNGNTAVAEGNKLTVTDQTKPVTPPSPE EPGAQEVHFSKVNVGGEEIAGAEIHIKQ⑶TWASWVSEAGKTHTLKLKPGHYIFHEAVAPGGYLAVTDIHFSVDET GQVTVTDVNGNTAVAEGNKLTVTDQTKPVTPPSPEEPGAQEVHFSKVNVGGEEIAGAEIHIKQ⑶TVVASWVSEAGK THTLKLKPGHYIFHEAVAPGGYLAVTDIHFSVDETGQVTVTDVNGNTAVAEGNKLTVTDQSADKDKQDKLPNTGETT GTYLSILGMITAVFASLLYRSKKK(SEQ ID NO 9)錨定-3包含分選酶底物基序LPNTG (SEQ ID NO 10),如上文SEQ ID NO 9中下劃 線所示。23F、INV200和0XC141還編碼非肺炎鏈球菌菌株INV104B編碼的額外的多肽序 列。這些額外的多肽序列在本文實(shí)施例2中描述,作為本文所述方法可用序列的具體例子, 以及作為在對(duì)象中產(chǎn)生抗體和/或刺激免疫應(yīng)答的免疫原性組合物中的抗原。mmmm^mn^m^mmm^f本文所述方法和組合物可用于菌毛多肽或來(lái)自任何革蘭氏陽(yáng)性菌的其他多 肽,所述革蘭氏陽(yáng)性菌包括例如,肺炎鏈球菌。在GAS(如釀膿鏈球菌(Streptococcus pyogenes)) (Mora 等,2005,Proc. Natl. Acad. Sci. USA, 102 15641-6),GBS (如,無(wú)乳鏈球菌 (Streptococcus agalactiae))(Lauer 等,2005,Science, 309 105 ;WO 2006/078318),內(nèi) 氏放線菌(Actinomycetes naeslundii) (Yeung 等,1998,Infect. Immun. ,66 1482-91),白 喉棒狀桿菌(Ton-That 等,2003,Mol. Microbiol. ,50 1429-38 ;Ton-That 和 Schneewind, 2004,Trends. Microbiol. , 12 :228_34),產(chǎn)氣莢膜梭菌(Clostridium perfringens)和 糞腸球菌(Enterococcus faecalis)中已經(jīng)鑒定到已知和推定的菌毛蛋白。革蘭氏陽(yáng)性菌的例子包括但不限于硬壁菌科,例如鏈球菌屬(Streptococcus)(如肺炎鏈球 菌(S. pneumoniae)、無(wú)乳鏈球菌(S. agalactiae)、釀膿鏈球菌(S. pyogenes)、豬鏈球 菌(S. suis)、獸疫鏈球菌(S. zoo印idemicus)、草綠色鏈球菌(S. viridans)、變形鏈球菌 (S.mutans)、格氏鏈球菌(S. gordonii)、馬鏈球菌(S. equi))、桿菌屬(Bacillus)(如炭 疽桿菌(B. anthracis)、蠟樣芽孢桿菌(B. cereus)、枯草桿菌(B. subtilis))、李斯特菌屬 (Listeria)(如無(wú)害李斯特菌(L. innocua)、單核細(xì)胞增生李斯特菌(L. monocytogenes))、 葡萄球菌屬(Staphylococcus)(如金黃色葡萄球菌(S. aureus)、表皮葡萄球菌 (S. epidermidis)、山 羊葡萄球菌(S. caprae)、腐生葡萄球菌(S. saprophyticus)、路鄧 葡萄球菌(S. Iugdunensis)、施氏葡萄球菌(S. schleiferi))、腸球菌屬(Enterococcus) (如糞腸球菌(E. faecal is)、屎腸球菌(E. faecium))、乳酸菌屬(Lactobacillus)、乳球 菌屬(Lactococcus)(如乳酸乳球菌(L. Iactis))、明串珠菌屬(Leuconostoc)(如腸膜明 串珠菌(L. mesenteroides))、梳狀菌屬(pectinatus)、片球菌屬(Pediococcus)、醋酸桿 菌屬(Acetobacterium)、梭菌屬(Clostridium)(如肉毒梭菌(C. botulinum)、艱難梭菌 (C. difficile)、產(chǎn)氣莢膜梭菌(C. perfringens)、破傷風(fēng)梭菌(C. tetani))、瘤胃球菌屬 (Ruminococcus)(如白色瘤胃球菌(R. albus))、螺旋桿菌屬(Heliobacterium)、草螺菌屬 (Heliospirillum)和鼠孢菌屬(Sporomusa);和放線菌科,例如放線菌屬(Actinomycetes) (如內(nèi)氏放線菌(A.naeslundii))、棒狀桿菌屬(Corynebacterium)(如白喉棒狀桿菌 (C. diphtheriae)、效力棒狀桿菌(C. eff iciens))、節(jié)桿菌屬(Arthrobacter)、雙岐桿菌 屬(Bifidobacterium)(如長(zhǎng)雙歧桿菌(B. Iongum))、弗蘭克菌屬(Frankia)、微球菌屬 (Micrococcus)、單孢絲菌屬(Micromonospora)、分枝桿菌屬(Mycobacterium)(如結(jié)核分 枝桿菌(M. tuberculosis)、麻風(fēng)分枝桿菌(M. 1印rae)、牛分枝桿菌(M. bovis)、非洲分枝 桿菌(M. africanum)、田鼠分枝桿菌(M. microti))、諾卡氏菌屬(Nocardia)(如星形諾卡 氏菌(N. asteroides))、丙酸桿菌屬(Propionibacteriun)禾口鏈霉菌屬(Streptomyces) (如索馬里鏈霉菌(S. somaliensis)、除蟲(chóng)鏈霉菌(S. avermitilis)、天藍(lán)色鏈霉菌 (S.coelicolor))。分離肽禾π其他,來(lái)mti^mmm^妝分離的肺炎鏈球菌多肽可用于本文所述的方法中,并用作在對(duì)象中產(chǎn)生抗體和/ 或刺激免疫應(yīng)答的免疫原性組合物中的抗原。有用的肺炎鏈球菌LPXTG細(xì)胞壁錨定菌毛 多肽的例子包括LPXTG-1、LPXTG-1A、LPXTG_2、錨定-1、錨定_2和錨定-3 (即SEQ ID NO 2、4、6、7、8和9)。有用的肺炎鏈球菌分選酶多肽的例子包括分選-1、分選_2、分選-23F 和分選-0XC141(即SEQ ID NO :676、1123、1386和282)。肺炎鏈球菌多肽的變體也可用于 本文所述的方法中,作為在對(duì)象中產(chǎn)生抗體和/或刺激免疫應(yīng)答的免疫原性組合物中的抗 原。例如,新方法中也可使用與肺炎鏈球菌多肽序列具有至少80%序列相同性,例如至少 85%、至少90%、至少95%、至少98%或至少99%相同性的肺炎鏈球菌多肽。而且,本文所 述的組合物和方法中可使用最多具有50個(gè),例如1、3、5、10、15、20、25、30或40個(gè)氨基酸插 入、刪除或取代,例如保守氨基酸取代的肺炎鏈球菌多肽序列。確定兩個(gè)氨基酸序列之間的相同性百分比可采用BLAST 2. O程序來(lái)完成,公眾可 WUncbi. nlm. nih. gov/BLAST獲得該程序。采用無(wú)缺口比對(duì)和默認(rèn)參數(shù)(BL0SUM 62矩陣, 存在缺口損耗為11,每個(gè)殘基缺口損耗為1,λ比率0.85)進(jìn)行序列比較。BLAST程序中采用的數(shù)學(xué)算法參見(jiàn) Altschul 等,1997,NucleicAcids Research, 25 :3389_3402。如本文所用,“保守氨基酸取代”表示多肽中的一個(gè)氨基酸家族內(nèi)的氨基酸取代。 氨基酸家族是本領(lǐng)域所明白的,基于氨基酸側(cè)鏈的物理和化學(xué)性質(zhì)進(jìn)行分類(lèi)。家族包括具 有堿性側(cè)鏈的氨基酸(例如,賴氨酸、精氨酸和組氨酸);具有酸性側(cè)鏈的氨基酸(例如,天 冬氨酸和谷氨酸);具有不帶電極性側(cè)鏈的氨基酸(例如,甘氨酸、天冬酰胺、谷胺酰胺、絲 氨酸、蘇氨酸、酪氨酸和半胱氨酸);具有非極性側(cè)鏈的氨基酸(例如,丙氨酸、纈氨酸、亮氨 酸、異亮氨酸、脯氨酸、苯丙氨酸、甲硫氨酸和色氨酸);具有分枝側(cè)鏈的氨基酸(例如,蘇氨 酸、纈氨酸和異亮氨酸);和具有芳族側(cè)鏈的氨基酸(例如,酪氨酸、苯丙氨酸、色氨酸和組 氨酸)。氨基酸可屬于一個(gè)以上的家族。肺炎鏈球菌多肽的片段,如免疫原性片段也可用于本文所述的方法和組合物中。 通常,該片段具有至少8、10、15、20、50、100、200或500個(gè)毗連的肺炎鏈球菌多肽的氨基酸 殘基。具有有用片段的肺炎鏈球菌LPXTG多肽的例子包括LPXTG-1、LPXTG-1A、LPXTG_2、錨 定-1、錨定-2或錨定-3 (例如,SEQ ID N0:2、4、6、7、8或9)。具有有用片段的肺炎鏈球菌 分選酶多肽的非限制性例子包括分選-1、分選_2、分選-23F和分選-0XC141 ( S卩,SEQ ID NO :676、1123、1386和282)。在一些實(shí)施方式中,這些片段保留至少一種全長(zhǎng)蛋白質(zhì)的生物 學(xué)活性,例如與肽聚糖細(xì)胞壁共價(jià)結(jié)合或能夠通過(guò)LPXTG基序與另一片段或蛋白質(zhì)交聯(lián)。
在一些實(shí)施方式中,本文所述的免疫原性組合物包含一種或多種可以寡聚體(菌 毛)形式配制或純化的肺炎鏈球菌菌毛多肽。在一些實(shí)施方式中,所述寡聚體形式是超寡 聚體。在一些實(shí)施方式中,本文所述的免疫原性組合物包含一種或多種以寡聚體(菌毛) 形式分離的肺炎鏈球菌菌毛多肽。所述包含肺炎鏈球菌菌毛多肽的寡聚體或超寡聚體菌毛 結(jié)構(gòu)可純化或以其他方式配制,以便用于免疫原性組合物中。一種或多種來(lái)自肺炎鏈球菌開(kāi)放閱讀框多核苷酸序列的肺炎鏈球菌多肽可以被 編碼替代ORF的片段的多核苷酸序列所替代。在一些實(shí)施方式中,一種或多種來(lái)自肺炎鏈 球菌開(kāi)放閱讀框的肺炎鏈球菌多肽可以被與替代ORF具有序列同源性的序列所替代。一種或多種肺炎鏈球菌菌毛多肽序列通常包含LPXTG基序(如LPXTG (SEQID NO 10))或其他分選酶底物基序。通常,肺炎鏈球菌菌毛蛋白的LPXTG分選酶底物基序可以 表示為通式 X1X2X3X4GGEQ ID NO :1746),其中 X1 是!^、V、E、Y、I、Q ;如果 X1 是!^,則 X2 是 P ;如果X1是E或Q則X2是V ;如果X1是V,則X2是V或P ;X3是任何氨基酸殘基;如果X1 是V、E或Q,則X4是T ;如果X1是L,則X4是T、S或A。LPXTG基序的非限制性例子包括 YPXTG (SEQ IDNO :11)、IPXTG (SEQ ID NO 12)、LPXSG (SEQ ID NO 13)、VVXTG (SEQ IDNO 14)、EVXTG (SEQ ID NO 15)、VPXTG (SEQ ID NO 16)、QVXTG (SEQ IDNO 17)、LPXAG (SEQ ID NO 18)、QVPTG(SEQ ID NO 19)、FPXTG(SEQ IDNO 20)禾口 VTXTG(SEQ ID NO :21)。本文所述的肺炎鏈球菌菌毛多肽可實(shí)現(xiàn)肺炎鏈球菌附著于上皮細(xì)胞并侵入上皮 細(xì)胞的功能。這些菌毛多肽也可能影響肺炎鏈球菌易位通過(guò)上皮細(xì)胞層的能力。在一些實(shí) 施方式中,一種或多種來(lái)自肺炎鏈球菌的肺炎鏈球菌菌毛多肽能夠結(jié)合或以其他方式聯(lián)接 于上皮細(xì)胞表面或其合成模型。在一些實(shí)施方式中,一種或多種肺炎鏈球菌菌毛多肽結(jié)合 或聯(lián)接于纖維蛋白原、纖連蛋白或膠原中的一種或多種。預(yù)測(cè)肺炎鏈球菌分選酶蛋白與含LPXTG的表面蛋白的分泌與錨定有關(guān)。本文所述 的肺炎鏈球菌菌毛I(xiàn)I島(INV104B)分選酶蛋白由對(duì)應(yīng)于TIGR4的SP1008和spl009的基因之間相同6. 5kb插入物中所見(jiàn)的基因(分選-1和分選_2)編碼,如上文LPXTG-I和LPXTG-2 基因所述。23F和0XC141也編碼分選酶分選_23F(SEQ ID NO 1386)和分選-0XC141 (SEQ ID NO :282)。本文所述方法中使用的分選酶蛋白和分選酶蛋白的變體可由革蘭氏陽(yáng)性菌獲得。肺炎鏈球菌菌毛多肽可通過(guò)膜結(jié)合的轉(zhuǎn)肽酶(如分選酶)共價(jià)連接于細(xì)菌細(xì) 胞壁。分選酶可用于切割表面蛋白,優(yōu)選在LPXTG基序的蘇氨酸和甘氨酸殘基之間。然 后,分選酶有助于在蘇氨酸羧基與細(xì)胞壁前體如脂質(zhì)II之間形成酰胺鍵。然后,該前體 通過(guò)細(xì)菌壁合成的轉(zhuǎn)糖基和轉(zhuǎn)肽反應(yīng)結(jié)合到肽聚糖中。參見(jiàn)Comfort等,Infection和 Immunity(2004)72(5) :2710_2722。在一些實(shí)施方式中,本文所述的組合物包含寡聚菌毛樣結(jié)構(gòu),所述寡聚菌毛樣結(jié) 構(gòu)包含肺炎鏈球菌菌毛多肽如LPXTG-I、LPXTG-1A、LPXTG_2、錨定_1、錨定_2或錨定-3 (如 SEQ ID N0:2、4、6、7、8或9)。寡聚菌毛樣結(jié)構(gòu)可包含許多菌毛多肽單元。在一些實(shí)施方式 中,寡聚菌毛樣結(jié)構(gòu)包含兩種或更多種菌毛蛋白。在一些實(shí)施方式中,寡聚菌毛樣結(jié)構(gòu)包含 超-寡聚菌毛樣結(jié)構(gòu),該結(jié)構(gòu)包含至少兩個(gè)(例如、2、3、4、5、6、7、8、9、10、11、12、13、14、15、 20、25、30、35、40、45、50、60、70、80、90、100、120、140、150、20 0 或更多個(gè))寡聚亞基,其中每 個(gè)亞基包含菌毛蛋白或其片段。寡聚亞基可通過(guò)菌毛蛋白基序內(nèi)的保守賴氨酸共價(jià)結(jié)合。 寡聚亞基可通過(guò)LPXTG基序共價(jià)結(jié)合,在一些實(shí)施方式中,可通過(guò)蘇氨酸或絲氨酸的氨基 酸殘基共價(jià)結(jié)合。肺炎鏈球菌菌毛多肽或其片段可結(jié)合到本文所述的寡聚菌毛樣結(jié)構(gòu)中,在一些實(shí) 施方式中,包含菌毛蛋白基序。寡聚菌毛樣結(jié)構(gòu)可以單獨(dú)使用或聯(lián)用。在一些實(shí)施方式中, 本文所述的組合物包含寡聚形式的肺炎鏈球菌菌毛I(xiàn)I島(INV104B)菌毛。并且,在一些實(shí) 施方式中,肺炎鏈球菌菌毛I(xiàn)I島(INV104B)菌毛可以超寡聚形式構(gòu)造。菌毛純化方法肺炎鏈球菌編碼的菌毛可以從表達(dá)肺炎鏈球菌菌毛或菌毛樣結(jié)構(gòu)的細(xì)胞,例如細(xì) 菌細(xì)胞純化,該過(guò)程包括例如通過(guò)機(jī)械剪切或酶消化從細(xì)胞分離菌毛,以及離析經(jīng)分離的 菌毛。用于純化菌毛的合適的細(xì)菌細(xì)胞包括表達(dá)肺炎鏈球菌菌毛多肽的有菌毛的革 蘭氏陽(yáng)性菌菌株,用一種或多種革蘭氏陽(yáng)性菌毛蛋白如肺炎鏈球菌LPXTG-1、LPXTG-1A、 LPXTG-2、錨定-1、錨定-2和錨定-3 (如SEQ ID NO :2、4、6、7、8和9)轉(zhuǎn)化的無(wú)菌毛的革 蘭氏陽(yáng)性菌,以及用一種或多種革蘭氏陽(yáng)性菌菌毛蛋白如肺炎鏈球菌LPXTG-1、LPXTG-1A、 LPXTG-2、錨定-1、錨定-2和錨定_3(如、SEQID NO :2、4、6、7、8和9)轉(zhuǎn)化的革蘭氏陰性或其 他細(xì)胞。通常,用于純化菌毛的細(xì)胞僅產(chǎn)生所需的菌毛類(lèi)型,例如內(nèi)源性或異源性菌毛。為 產(chǎn)生異源性菌毛,通過(guò)例如突變或重組DNA方法改變細(xì)胞,使其不產(chǎn)生內(nèi)源性菌毛。通常, 可用于純化的產(chǎn)生菌毛的革蘭氏陽(yáng)性菌細(xì)胞將表達(dá)一種或多種相容的分選酶,使得菌毛在 細(xì)胞表面表達(dá)。可進(jìn)行純化的肺炎鏈球菌菌毛I(xiàn)I島(INV104B)、23F、INV200和0XC141LPXTG 細(xì)胞壁錨定多肽的例子包括LPXTG-1、LPXTG-1A、LPXTG_2、錨定-1、錨定_2和錨定_3(如、 SEQ ID NO :2、4、6、7、8和9)??蛇M(jìn)行純化的肺炎鏈球菌菌毛I(xiàn)I島(INV104B)、23F、INV200 和0XC141分選酶的例子包括分選-1、分選_2、分選-23F和分選-0XC141 (如SEQ ID NO 676、1123、1386 和 282)。
從革蘭氏陽(yáng)性菌細(xì)胞分離菌毛通常通過(guò)機(jī)械剪切、酶消化、降低或抑制分選酶活 性,或用干擾細(xì)胞壁完整性的化合物進(jìn)行處理來(lái)實(shí)現(xiàn)。機(jī)械剪切可從細(xì)胞物理去除菌毛,而 其他方法可消除菌毛連接點(diǎn)(例如,通過(guò)降解細(xì)胞壁或菌毛組分)。從細(xì)胞分離菌毛之后, 菌毛和細(xì)胞可通過(guò)離心分離。 機(jī)械剪切方法的非限制性例子包括超聲處理、玻璃珠剪切和混合。超聲處理的 方法例如在Yamaguchi等,2004,Current Microbiol.,49 :59_65中討論。玻璃珠剪切方 法例如在Levesque等,2001,J. Bacteriol.,183 =2724-32中討論。機(jī)械剪切的一般方法 例如在 Wolfgang 等,1998,Mol. Microbiol.,29 321-30 ;Trachtenberg 等,2005,J. Mol. Biol.,346 665-676 ;Parge 等,1990,J. Biol. Chem.,265 :2278_85 ;Isaacson 等,1981, J. Bacteriol.,146 784-9 ;Korhonen 等,1980,Infect. Immun. ,27 :569_75 ;Hahn 等,2002, J. Mol. Biol.,323 :845_57 ;St. Geme 等,1996,Proc. Natl. Acad. Sci. USA, 93 :11913_18 ; Weber 等,2005,J. Bacteriol.,187 :2458_68 ;和 Mu 等,2002,J. Bacteriol.,184 :4868_74 中討論。適用于酶消化的酶的非限制性例子包括細(xì)胞壁降解酶,例如變?nèi)芫?、溶葡?球菌素和溶菌酶。酶消化的方法例如在Bender等,2003,J. Bacteriol.,185 :6057_66 ; Ton-That 等,2004,Mol. Microbiol. ,53 :251_61 ;和 Ton-That 等,2003,Mol. Microbiol., 50 1429-38中討論。對(duì)于下游給予對(duì)象,可采用多種酶以去除可能造成不希望的宿主反應(yīng) 的細(xì)胞壁組分。抑制或降低分選酶活性的方法的非限制性例子包括通過(guò)引入SrtA失能等位基 因、刪除內(nèi)源性SrtA基因、表達(dá)降低SrtA表達(dá)的核酸(例如,反義或miRNA)以及用抑制 SrtA活性的化合物處理細(xì)胞來(lái)降低SrtA活性(參見(jiàn)例如,Marrafini等,Microbiol. Mol. Biol. Rev. ,70 :192_221,2006)。示例性的分選酶A抑制劑包括甲烷-硫代磺酸酯(如,MTSET和(2_磺酸基乙基) 甲燒-硫代磺酸酯)(Ton-That 和 Schneewind,J. Biol. Chem.,274 :24316_24320,1999), 對(duì)羥基汞苯甲酸,葡糖基留醇β-谷固醇-3-0-吡喃葡糖醇(Kim等,Biosci. Biotechnol. Biochem.,67 :2477_79,2003),氯化黃連素(Kim 等,Biosci. Biotechnol. Biochem.,68 421-24,2004),肽基-重氮甲燒(LPAT-CHN2) (Scott 等,Biochem. J.,366 :953_58,2002), 肽基 _ 氯甲烷(LPAT-CH2C1),肽基-乙烯砜[LPAT-SO2(Ph)] (Conolly 等,J. Biol. Chem., 278 :34061-65,2003),乙烯砜(如,二 -、乙基-、甲基-和苯基乙烯砜)(Frankel等,J. Am. Chem. Soc. ,126 :3404_3405,2004),蘇氨酸殘基被膦酸酯基團(tuán)取代的LPXTG基序肽(如, LPEΨ (PO2H-CH2IG) (Kruger 等,Bioorg. Med. Chem.,12 :3723_29,2004),取代的(Z)- 二 芳基丙烯腈(Oh等,J. Med. Chem. ,47 =2418-21,2004)和各種藥用植物的提取物(Kim等, Biosci.Biotechnol. Biochem.,66 :2751_54,2002)。干擾細(xì)胞壁完整性的化合物的非限制性例子包括甘氨酸和抗生素,例如青霉素 (如甲氧西林、阿莫西林、氨芐青霉素)、頭孢菌素(如頭孢氨芐、頭孢丙烯、頭孢吡肟)、糖肽 (如去甲萬(wàn)古霉素、替考拉寧、雷莫拉寧)和環(huán)絲氨酸。分離的菌毛可通過(guò)密度,例如采用密度梯度離心而與其他組分分離。例如,菌毛可 通過(guò)蔗糖梯度離心而分離。通常,由于菌毛中存在不同數(shù)量的菌毛蛋白亞基,含革蘭氏陽(yáng)性菌毛的樣品將包含不同分子量的菌毛寡聚體。為了降低多分散性,可根據(jù)大小分離含革蘭氏陽(yáng)性菌毛的樣 品。例如,可采用凝膠過(guò)濾柱或大小排阻柱。也可使用超濾膜來(lái)降低多分散性??刹捎糜H和方法如親和色譜法分離革蘭氏陽(yáng)性菌毛。例如,將特異性結(jié)合革蘭氏 陽(yáng)性菌毛的蛋白質(zhì),如特異性結(jié)合菌毛組分的抗體或優(yōu)先結(jié)合菌毛的抗體固定到固相基質(zhì) (例如色譜基質(zhì))上,然后使含革蘭氏陽(yáng)性菌毛的樣品曝露于固定的結(jié)合蛋白質(zhì)。這種親和 分離方法也可用于分離、純化或富集表達(dá)革蘭氏陽(yáng)性菌毛的細(xì)胞制品。
革蘭氏陽(yáng)性菌毛也可采用本領(lǐng)域已知的任何其他蛋白純化方法,例如沉淀、柱色 譜方法和樣品濃縮方法進(jìn)行分離。其他方法例如參見(jiàn)RufTolo等,1997,Infect. Immun., 65:339-43。蛋白純化方法詳見(jiàn)于Scopes,R. K.,《蛋白質(zhì)純化原理與實(shí)踐》(Protein Purification Principles and Practice),第 3 片反,1994, Springer, NY。純化期間組分中出現(xiàn)革蘭氏陽(yáng)性菌毛后可進(jìn)行電泳(如聚丙烯酰胺電泳),測(cè)定 特異性結(jié)合革蘭氏陽(yáng)性菌毛的試劑(例如,針對(duì)菌毛蛋白的抗體或優(yōu)先結(jié)合菌毛的抗體) 的結(jié)合,和/或測(cè)定菌毛活性,例如蛋白質(zhì)或細(xì)胞結(jié)合活性。Si^本文所述的肺炎鏈球菌多肽也可用于制備針對(duì)這些肺炎鏈球菌多肽的特異性抗 體。在一些實(shí)施方式中,抗體對(duì)寡聚體或超寡聚體形式的肺炎鏈球菌菌毛多肽是特異性的。 本文所述的組合物也可包含肺炎鏈球菌菌毛多肽與選擇的其他肺炎鏈球菌多肽的特異性 抗體的組合,以提供針對(duì)范圍擴(kuò)大的血清型和菌株分離物的保護(hù)作用。例如,這種組合可包 含第一和第二抗體,其中所述第一抗體是對(duì)第一肺炎鏈球菌多肽特異性的,第二抗體是對(duì) 第二肺炎鏈球菌多肽或非_肺炎鏈球菌多肽特異性的。本文所述的特異性肺炎鏈球菌多肽抗體包括一個(gè)或多個(gè)能夠通過(guò)化學(xué)或物理方 式結(jié)合于或聯(lián)接于肺炎鏈球菌多肽的表位的生物學(xué)部分。本文所述抗體包括特異性結(jié)合 肺炎鏈球菌多肽的抗體。本文所述組合物包含由多克隆和單克隆制劑獲得的抗體,以及以 下物質(zhì)雜交(嵌合)抗體分子(參見(jiàn)例如,Winter等,(1991) Nature 349 =293-299 ;和美 國(guó)專(zhuān)利4,816,567 ;F(ab,)2和F(ab)片段;Fv分子(非共價(jià)異二聚體,參見(jiàn)例如,Inbar 等,(1972)Proc Natl Acad Sci USA 69 :2659_2662 ;和 Ehrlich 等,(1980)Biochem 19: 4091-4096);單鏈 Fv 分子(sFv)(參見(jiàn)例如,Huston 等,(I988)Proc Natl Acad Sci USA 85 =5897-5883) ;二聚和三聚抗體片段構(gòu)建物;小抗體(參見(jiàn)例如,Pack等,(1992)Biochem 31 1579-1584 ;Cumber 等,(1992) JImmunology 149B 120-126);人源化抗體分子(參見(jiàn) 例如,Riechmann 等,(1988) Nature 332 :323_327 ;Verhoeyan 等,(1988) Science 239 1534-1536 ;和英國(guó)專(zhuān)利公開(kāi)GB 2,276,169,1994年9月21日出版);以及從這些分子獲得 的任何功能性片段,其中所述片段保留母體抗體分子的免疫結(jié)合性質(zhì)。本文所述的組合物 還包含通過(guò)非常規(guī)方法,例如噬菌體展示獲得的抗體。本文所述的抗體可以是多克隆、單克隆、重組(例如嵌合或人源化)的完全人、非 人(例如鼠)或單鏈抗體。這些抗體的制備方法是已知的。在一些情況下,抗體具有效應(yīng) 功能并能固定補(bǔ)體(fix complement) 0抗體也可偶聯(lián)毒素、報(bào)道基團(tuán)或成像試劑。在一些實(shí)施方式中,本文所述的特異性肺炎鏈球菌抗體是單克隆抗體。這些單 克隆抗體包括具有均一抗體群的抗體組合物。本文所述的單克隆抗體可以從鼠雜交瘤獲 得,采用人而非鼠雜交瘤獲得人單克隆抗體。例如參見(jiàn)Cote等,單克隆抗體和癌癥治療(Monoclonal Antibodies and Cancer Therapy),Alan R· Liss,1985,第 77 頁(yè)。嵌合、人源化(例如完全人)的抗體適合需要重復(fù)給予人對(duì)象的情況,例如治療性 應(yīng)用(以及一些診斷應(yīng)用)。本文所述的抗體也可用于肺炎鏈球菌感染的預(yù)防或治療應(yīng)用。該抗體可阻斷肺炎 鏈球菌附著于宿主細(xì)胞或?qū)λ拗骷?xì)胞的一些其他活性。此外,抗體還可用于將毒素或治療 劑(如抗生素)遞送至肺炎鏈球菌細(xì)胞。本文所述的抗體可用于診斷應(yīng)用,例如,用于檢測(cè)生物樣品中是否存在肺炎鏈球 菌多肽。來(lái)自肺炎鏈球菌抗體的抗-纖絲、菌毛多肽或其他多肽可用于診斷目的,以監(jiān)測(cè)組 織中的蛋白質(zhì)水平作為臨床試驗(yàn)過(guò)程的一部分,例如以測(cè)定給定治療方案的效力。將抗體 偶聯(lián)(例如物理連接)于可檢測(cè)物質(zhì)(即抗體標(biāo)記)以便于檢測(cè)??蓹z測(cè)物質(zhì)的例子包 括各種酶、輔基、熒光材料、造影劑、發(fā)光材料、生物發(fā)光材料和放射性材料。合適的酶的 例子包括辣根過(guò)氧化物酶、堿性磷酸酶、β -半乳糖苷酶或乙酰基膽堿酯酶;合適的輔基復(fù) 合物的例子包括鏈霉親和素/生物素和親和素/生物素;合適的熒光材料的例子包括傘形 酮、熒光素、熒光素異硫氰酸酯、羅丹明、二氯三嗪胺熒光素、丹酰氯或藻紅蛋白;造影劑的 例子包括適合電鏡鏡檢的電子致密材料如金顆粒、或適合磁共振成象的磁活性材料如超磁 性(supermagnetic)鐵顆粒;發(fā)光材料的例子包括發(fā)光氨( luminol);生物發(fā)光材料的例子 包括螢光素酶、螢光素和水母素;合適的放射性材料的例子包括125I、131I、35S或3H。檢測(cè)受 感染患者,例如測(cè)定來(lái)自患者的樣品中是否存在含肺炎鏈球菌菌毛I(xiàn)I島(INV104B)菌毛的 有菌毛肺炎鏈球菌的方法中可使用這些診斷抗體。然后基于肺炎鏈球菌的存在情況選擇療 程。例如,被無(wú)菌毛的肺炎鏈球菌感染的患者可用抗生素進(jìn)行治療,而被含有肺炎鏈球菌菌 毛多肽的有菌毛肺炎鏈球菌感染的患者可用菌毛結(jié)合化合物,如抗體和/或抗炎藥(如, IL-6或抗-TNF試劑如抗TNF抗體)進(jìn)行治療。篩選試驗(yàn)在一些方面,本文所述方法(在這里也稱(chēng)為“篩選試驗(yàn)”)可用于鑒定調(diào)節(jié)劑,即從 一種或多種測(cè)試化合物(例如,抗體、蛋白質(zhì)、肽、肽模擬物、類(lèi)肽、無(wú)機(jī)小分子、非核酸類(lèi)有 機(jī)小分子、核酸(如反義核酸、siRNA、寡核苷酸或合成寡核苷酸)、或其他藥物)鑒定的抑 制肺炎鏈球菌菌毛多肽的活性(如結(jié)合活性)的候選化合物或試劑。這樣鑒定的化合物可 用于調(diào)節(jié)含肺炎鏈球菌菌毛多肽的肺炎鏈球菌的結(jié)合活性,或者在治療方案中這種肺炎鏈 球菌的粘附,以調(diào)整肺炎鏈球菌的生物學(xué)功能。在一些實(shí)施方式中,提供篩選測(cè)試化合物以鑒定結(jié)合肺炎鏈球菌菌毛多肽或其一 部分的那些化合物的試驗(yàn)??蓽y(cè)定結(jié)合肺炎鏈球菌菌毛多肽的化合物調(diào)節(jié)肺炎鏈球菌菌毛 相關(guān)活性,例如粘附、感染或者炎癥反應(yīng)的能力。本文所述方法中使用的測(cè)試化合物可利用本領(lǐng)域已知的許多組合文庫(kù)方法中的 任一種獲得,包括生物學(xué)文庫(kù);類(lèi)肽文庫(kù)(具有肽功能,但具有新型非肽主鏈的文庫(kù),其 不發(fā)生酶降解,但仍然保持生物活性;參見(jiàn)例如,Zuckermann等,1994,J. Med. Chem. ,37 2678-2685);空間可尋址的平行固相或溶液相文庫(kù);要求解卷積的合成文庫(kù)方法;“一珠 一化合物”的文庫(kù)方法;和利用親和色譜選擇的合成文庫(kù)方法。生物學(xué)文庫(kù)和類(lèi)肽文庫(kù)方 法限于肽文庫(kù),而其他四種方法適用于肽、非肽寡聚體或小分子化合物的文庫(kù)(Lam,1997, Anticancer Drug Des. ,12 145)。
本領(lǐng)域中分子文庫(kù)合成方法的例子可參見(jiàn)例如=DeWitt等,(1993,Proc. Natl. Acad. Sci. USA, 90 6909 ;Erb φ, 1994, Proc. Natl. Acad. Sci. USA, 91 -.11422 ;Zuckermann 等,1994,J. Med. Chem. ,37 2678 ;Cho 等,1993,Science, 261 1303 ;Carre 11 等,1994, Angew. Chem. Int. Ed. Engl. , 33 :2059 ;Care 11 等,1994, Angew. Chem. Int. Ed. Engl. , 33 2061 ;和 in Gallop 等,1994,J. Med. Chem. ,37 :1233)?;衔镂膸?kù)可以存在于溶液中(如,Houghten,1992,Biotechniques,13 412-421),或珠上(Lam, 1991, Nature, 354 82-84),芯片上(Fodor, 1993, Nature, 364 555-556),細(xì)菌中(Ladner,美國(guó)專(zhuān)利 5,223,409),孢子中(Ladner,美國(guó)專(zhuān)利 5,223,409), 質(zhì)粒中(Cull 等,1992,Proc. Natl. Acad. Sci. USA,89 1865-1869),或噬菌體上(Scott 和 Smith,1990,Science,249 386-390 ;Devlin,1990, Science, 249 404-406 ;Cwirla 等,1990,Proc. Natl. Acad. Sci. USA, 87 :6378_6382 ;Felici,1991,J. Mol. Biol.,222 301-310 ;和 Ladner 同上)。在一些實(shí)施方式中,試驗(yàn)是基于細(xì)胞的試驗(yàn),其中表達(dá)肺炎鏈球菌多肽或其生物 活性部分的細(xì)胞(例如細(xì)菌細(xì)胞)與測(cè)試化合物相接觸,例如通過(guò)監(jiān)測(cè)細(xì)胞結(jié)合,測(cè)定測(cè)試 化合物調(diào)節(jié)肺炎鏈球菌活性的能力。例如,細(xì)胞可以是哺乳動(dòng)物來(lái)源,例如鼠、大鼠、或人來(lái) 源。細(xì)胞可以是上皮細(xì)胞,例如A549肺上皮細(xì)胞。 例如,通過(guò)在化合物(例如底物)上偶聯(lián)放射性同位素或酶標(biāo)記,使得可通過(guò)檢測(cè) 復(fù)合物中的標(biāo)記化合物(例如底物)來(lái)確定化合物(例如底物)與肺炎鏈球菌菌毛I(xiàn)I島 (INV104B)菌毛或菌毛蛋白的結(jié)合,從而評(píng)價(jià)測(cè)試化合物調(diào)節(jié)肺炎鏈球菌菌毛多肽與配體 或底物,例如細(xì)胞或蛋白質(zhì)如纖維蛋白原、纖連蛋白或膠原結(jié)合的能力?;蛘?,可將肺炎鏈 球菌多肽偶聯(lián)于放射性同位素或酶標(biāo)記,以監(jiān)測(cè)測(cè)試化合物調(diào)節(jié)肺炎鏈球菌多肽與底物結(jié) 合形成復(fù)合物的能力。例如,用125I、35S、14C或3H直接或間接標(biāo)記化合物(如,肺炎鏈球菌 多肽結(jié)合伴侶),并通過(guò)放射發(fā)射直接計(jì)數(shù)或通過(guò)閃爍計(jì)數(shù)檢測(cè)放射性同位素?;蛘撸捎?辣根過(guò)氧化物酶、堿性磷酸酶或熒光素酶酶法標(biāo)記化合物,并通過(guò)測(cè)定合適底物向產(chǎn)物的 轉(zhuǎn)化檢測(cè)酶標(biāo)記??稍u(píng)價(jià)化合物與具有或不具有任何相互反應(yīng)物標(biāo)記的肺炎鏈球菌多肽發(fā)生相互 作用的能力。例如,可利用顯微生理機(jī)能檢測(cè)儀來(lái)檢測(cè)化合物與肺炎鏈球菌多肽的相互作 用,化合物或肺炎鏈球菌多肽均未標(biāo)記(McConnell等,1992,Science257 1906-1912)。在
本文中,“顯微生理機(jī)能檢測(cè)儀”(如,Cytosensor )是利用光可尋址的電位測(cè)定傳感器 (LAPS)測(cè)量細(xì)胞酸化其環(huán)境的速率的分析儀器。這種酸化速率的改變可用作化合物與肺炎 鏈球菌多肽相互作用的指標(biāo)。在一些實(shí)施方式中,提供一種無(wú)細(xì)胞試驗(yàn),其中肺炎鏈球菌多肽或其生物活性部 分與測(cè)試化合物相接觸,并評(píng)價(jià)測(cè)試化合物與肺炎鏈球菌多肽或其生物活性部分結(jié)合的能 力。通常,新型試驗(yàn)中使用的肺炎鏈球菌多肽的生物活性部分包括參與與其他肺炎鏈球菌 多肽分子相互作用的片段。無(wú)細(xì)胞試驗(yàn)包括在足以使兩種組分相互作用和結(jié)合的條件和時(shí)間下制備靶基因 蛋白和測(cè)試化合物的反應(yīng)混合物,從而形成可以去除和/或檢測(cè)的復(fù)合物。可采用熒光能量轉(zhuǎn)移(FET)來(lái)檢測(cè)兩種分子間的相互作用(參見(jiàn)例如,Lakowicz 等,美國(guó)專(zhuān)利5,631,169和Stavrianopoulos等,美國(guó)專(zhuān)利4,868,103)。選擇第一“供體”分子上的熒光團(tuán)標(biāo)記,使其發(fā)射的熒光能量被第二 “接受體”分子上的熒光標(biāo)記吸收,所述 第二“接受體”分子由于吸收能量而發(fā)出熒光?;蛘撸敖邮荏w”蛋白分子可簡(jiǎn)單地利用色氨 酸殘基的天然熒光能量。選擇發(fā)射不同波長(zhǎng)光的標(biāo)記,使得“接受體”分子標(biāo)記區(qū)別于“供 體”分子標(biāo)記。由于標(biāo)記間的能量轉(zhuǎn)移效率與分子間隔距離有關(guān),所以可評(píng)價(jià)分子間的空間 關(guān)系。在分子間發(fā)生結(jié)合的情況下,試驗(yàn)中“接受體”分子標(biāo)記的熒光發(fā)射量最大。采用本 領(lǐng)域公知的標(biāo)準(zhǔn)熒光檢測(cè)技術(shù)(例如,采用熒光計(jì))可方便地測(cè)定FET結(jié)合事件。在一些實(shí)施方式中,采用實(shí)時(shí)生物分子相互作用試驗(yàn)(BIA)確定肺炎鏈球菌多肽 結(jié)合靶分子(例如纖維蛋白原、纖連蛋白、或膠原多肽或其片段)的能力(如,Sjolander 等,1991,Anal. Chem.,63 :2338-2345 和 Szabo 等,1995,Curr . Opin. Struct. Biol.,5 699-705)。“表面等離振子共振”或“ΒΙΑ”實(shí)時(shí)檢測(cè)生物特異性相互作用,無(wú)需標(biāo)記任何相 互作用物(例如,BIAcore) 0結(jié)合表面的質(zhì)量變化(表明發(fā)生結(jié)合)導(dǎo)致該表面附近光折 射率的改變(表面等離振子共振(SPR)的光學(xué)現(xiàn)象),產(chǎn)生可用于指示生物分子之間實(shí)時(shí)反 應(yīng)的可檢測(cè)信號(hào)。在一些實(shí)施方式中,將靶基因產(chǎn)物或測(cè)試物質(zhì)錨定到固相上。錨定到固相上的靶 基因產(chǎn)物/測(cè)試化合物復(fù)合物可以在反應(yīng)結(jié)束時(shí)檢測(cè)。靶基因產(chǎn)物可錨定到固體表面上, 而不發(fā)生錨定的測(cè)試化合物可用本文所述可檢測(cè)標(biāo)記進(jìn)行直接或間接標(biāo)記。多種靶基因產(chǎn)物可采用蛋白微陣列技術(shù)錨定到固相上,這種技術(shù)也稱(chēng)為蛋白芯片 技術(shù)或固相蛋白陣列技術(shù)。蛋白微陣列技術(shù)是本領(lǐng)域普通技術(shù)人員所熟知的,可包括但不 限于,獲得在固定基板上包含已鑒定肽或蛋白質(zhì)的陣列,使靶分子或生物組分與肽結(jié)合,并 評(píng)價(jià)這種結(jié)合。例如參見(jiàn),G. MacBeath和S. L. Schreiber,將蛋白質(zhì)印刷成微陣列以進(jìn)行 高通量功能測(cè)定("Printing Proteins asMicroarrays for High-Throughput Function Determination”),Science289 (5485) :1760_1763,2000。微陣列基板包括但不限于玻璃、 二氧化硅、鋁硅酸鹽、硼硅酸鹽、金屬氧化物如氧化鋁和氧化鎳、各種粘土、硝基纖維素或尼 龍??梢杂没衔锇晃㈥嚵谢逡源龠M(jìn)基板上探針(例如肽)的合成?;迳系呐悸?lián)劑 或基團(tuán)可用于將第一氨基酸共價(jià)連接到基板。本領(lǐng)域技術(shù)人員已知許多偶聯(lián)劑或基團(tuán)???以在基板上預(yù)定的柵格中直接合成肽探針。或者,可以在基板上點(diǎn)標(biāo)肽探針,在這種情況下 可用化合物包被基板以提高探針與基板的結(jié)合。在這些實(shí)施方式中,將預(yù)先合成的探針以 精確的預(yù)定體積和柵格圖案施加到基板上,優(yōu)選利用計(jì)算機(jī)控制的機(jī)器設(shè)備以接觸_印刷 方式或以非接觸方式(例如噴墨或壓電遞送)將探針施加到基板上。探針可共價(jià)連接于基 板。在一些實(shí)施方式中,可將一種或多種對(duì)照肽或蛋白分子連接到基板。對(duì)照肽或蛋白分 子能夠確定諸如肽或蛋白質(zhì)質(zhì)量和結(jié)合特性、反應(yīng)試劑質(zhì)量和有效性、雜交成功率以及分 析閾值和成功率等方面的因素。在一些實(shí)施方式中,希望固定肺炎鏈球菌多肽、抗-菌毛抗體或菌毛蛋白抗體,或 肺炎鏈球菌多肽結(jié)合蛋白以促進(jìn)上述一種或兩種蛋白質(zhì)復(fù)合形式與非復(fù)合形式的分離,并 且適應(yīng)分析自動(dòng)化。測(cè)試化合物與肺炎鏈球菌多肽的結(jié)合,或者在有或沒(méi)有候選化合物的 情況下肺炎鏈球菌多肽與靶分子的相互作用可以在適合包含這些反應(yīng)試劑的任何容器內(nèi) 完成。這些容器的例子包括微量滴定板、試管和微量離心管。在一個(gè)實(shí)施方式中,可提供 增加使得上述一種或兩種蛋白與基質(zhì)結(jié)合的結(jié)構(gòu)域的融合蛋白。例如,谷胱甘肽-S-轉(zhuǎn)移 酶/菌毛I(xiàn)I島(INV104B)菌毛蛋白融合蛋白或谷胱甘肽-S-轉(zhuǎn)移酶/靶標(biāo)融合蛋白可吸附到谷胱甘肽瓊脂糖(S印harose) 珠上(密蘇里州圣路易斯的西格瑪化學(xué)品公司(Sigma Chemical, St. Louis,MO)或谷胱甘肽衍生的微量滴定板上,然后混合測(cè)試化合物,或者混合 測(cè)試化合物與未吸附的靶蛋白或肺炎鏈球菌菌毛I(xiàn)I島(INV104B)菌毛或菌毛蛋白,在誘導(dǎo) 復(fù)合物形成的條件下孵育該混合物(例如,在鹽和PH的生理學(xué)條件下)。孵育后,洗滌珠 或微量滴定板以去除未結(jié)合的組分,對(duì)于珠的情況,例如如上所述直接或間接測(cè)定基質(zhì)固 定的復(fù)合物?;蛘?,復(fù)合物可與基質(zhì)解離,并用標(biāo)準(zhǔn)技術(shù)測(cè)定肺炎鏈球菌多肽結(jié)合或活性水 平。將肺炎鏈球菌多肽或結(jié)合靶標(biāo)固定到基質(zhì)上的其他技術(shù)包括利用生物素和親和 素的偶聯(lián)??衫帽绢I(lǐng)域已知的技術(shù)由生物素_NHS(N-羥基-琥珀酰亞胺)制備生物素 化的肺炎鏈球菌多肽或靶分子(例如,伊利諾斯州羅克福德的皮爾斯化學(xué)品公司(Pierce Chemicals, Rockford, IL)的生物素化試劑盒),并固定到鏈霉親和素包被的96孔板的各孔 中(皮爾斯化學(xué)品公司(Piece Chemical))。為進(jìn)行試驗(yàn),將非固定的組分加到含有錨定組分的包被表面上。反應(yīng)完全后,在任 何形成的復(fù)合物保持固定在固相表面的條件下去除未反應(yīng)的組分(例如通過(guò)洗滌)。錨定 在固相表面上的復(fù)合物的檢測(cè)可采用多種方式進(jìn)行。如果先前所述非固定的組分是預(yù)先標(biāo) 記的,則檢測(cè)到固定在固相表面上的標(biāo)記表明形成復(fù)合物。如果先前所述非固定的組分未 經(jīng)預(yù)先標(biāo)記,可利用間接標(biāo)記來(lái)檢測(cè)錨定在表面上的復(fù)合物;例如利用標(biāo)記的固定組分的 特異性抗體(該抗體又可用標(biāo)記的抗Ig抗體直接標(biāo)記或間接標(biāo)記)。在一些實(shí)施方式中,試驗(yàn)采用能夠特異性結(jié)合肺炎鏈球菌多肽或結(jié)合靶標(biāo),但不 會(huì)干擾肺 炎鏈球菌多肽與其靶標(biāo)的結(jié)合的抗體??蓪⑦@些抗體引入培養(yǎng)板各孔中,未結(jié)合 的靶標(biāo)或肺炎鏈球菌多肽通過(guò)抗體偶聯(lián)作用而被俘獲在各孔中。檢測(cè)這些復(fù)合物的方法除 了上述GST固定復(fù)合物方法之外,還包括利用與肺炎鏈球菌多肽或靶分子反應(yīng)的抗體免疫 檢測(cè)復(fù)合物,以及依賴于檢測(cè)與肺炎鏈球菌多肽或靶分子相關(guān)的酶活性的酶聯(lián)免疫分析。在一些實(shí)施方式中,在液相中進(jìn)行無(wú)細(xì)胞試驗(yàn)。在這種試驗(yàn)中,通過(guò)許多標(biāo)準(zhǔn)技 術(shù)將反應(yīng)產(chǎn)物與未反應(yīng)的組分分離,這些技術(shù)包括但不限于差速離心(例如,Rivas等, 1993,Trends Biochem. Sci.,18 :284_287);色譜(凝膠過(guò)濾色譜,離子交換色譜);電 泳(如,Ausubel等編,1999,《新編分子生物學(xué)方案》(CurrentProtocols in Molecular BioIory),J. Wiley 紐約);和免疫沉淀(例如,Ausubel等編,1999,《新編分子生物學(xué)方 案》,J.Wiley:紐約)。這些樹(shù)脂和色譜技術(shù)是本領(lǐng)域技術(shù)人員已知的(例如,Heegaard, 1998,J. Mol. Recognit. ,11 141-148 禾口 Hage 等,1997, J. Chromatogr. B. Biomed. Sci. Appl.,699 :499-525)。而且,如本文所述,也可方便地采用熒光能量轉(zhuǎn)移技術(shù)來(lái)檢測(cè)結(jié)合, 而無(wú)需從溶液進(jìn)一步純化復(fù)合物。在一些實(shí)施方式中,該試驗(yàn)包括使肺炎鏈球菌菌毛多肽或其生物活性部分與結(jié)合 肺炎鏈球菌菌毛多肽的已知細(xì)胞或化合物(如,蛋白質(zhì))相接觸,以形成試驗(yàn)混合物,使該 試驗(yàn)混合物與測(cè)試化合物相接觸,并測(cè)定測(cè)試化合物影響肺炎鏈球菌菌毛多肽與該細(xì)胞或 化合物結(jié)合的能力。測(cè)定與表達(dá)肺炎鏈球菌菌毛I(xiàn)I島(INV104B)菌毛的細(xì)菌細(xì)胞結(jié)合的試驗(yàn)通常包 括將表達(dá)肺炎鏈球菌菌毛I(xiàn)I島(INV104B)菌毛的細(xì)菌細(xì)胞與A549肺上皮細(xì)胞一起孵育, 洗滌以去除未貼附的細(xì)菌細(xì)胞,并檢測(cè)貼附的細(xì)菌細(xì)胞。細(xì)菌貼附可通過(guò)本領(lǐng)域的任何方式進(jìn)行測(cè)定,例如檢測(cè)抗體與貼附的細(xì)菌細(xì)胞的結(jié)合,或者裂解上皮細(xì)胞并對(duì)相結(jié)合的細(xì)菌細(xì)胞進(jìn)行計(jì)數(shù)。表達(dá)肺炎鏈球菌菌毛I(xiàn)I島(INV104B)菌毛的細(xì)菌細(xì)胞的結(jié)合試驗(yàn)中也 可使用HEP2細(xì)胞、CHO細(xì)胞或HeLa細(xì)胞。免疫原性組合物本文所述的免疫原性組合物除肺炎鏈球菌多肽外還可包含一種或多種抗原性物 質(zhì)。示例性的抗原包括下面列出的那些。此外,本文所述組合物可用于治療或預(yù)防任何下 述微生物導(dǎo)致的感染。免疫原性組合物中使用的抗原包括但不限于一種或多種以下抗原, 或者由一種或多種以下抗原衍生的抗原細(xì)菌抗原腦膜炎奈瑟菌(N. meningitides)來(lái)自腦膜炎萘瑟菌血清型A、C、W135、Y和 / 或B 的蛋白質(zhì)抗原(Bruyn, G. A. W.和 van Furth, R. (1991) Eur. J. Clin. Microbiol. Infect. Dis. 10,897-910 ;Ryan, M. W.和 Antonelli,P. J. (2000)Laryngoscope 110, 961-964 ;Cutts, F. Τ. , Zaman, S. Μ. , Enwere, G. , Jaffar, S. , Levine, 0. S. , Okoko,
C.Oluwalana, Α. , Vaughan, S. , Obaro, Α. , Leach, Α.等,(2005)Lancet365,1139-1146 ; Swiatlo, Ε. , Champlin, F. R. , HoIman, S. C. , Wilson, W. W. &ffatt, J. Μ. (2002) Infect. Immun. 70, 412-415 ;Sandgren, Α. , Albiger, B. , Orihuela, C. , Tuomanen, Ε. , Normark, S.禾口 Henriques-Normark,B. (2005)J.Infect. Dis. 192,791—800 ;Henriques Normark, B. , Christensson, B. , Sandgren, Α. , Noreen, B. , Sylvan, S. , Burman, L. G.禾口 Olsson-Liljequist, B. (2003)Microb. Drug Resist. 9,337-344 ;Nunes, S. , Sa-Leao, R-, Carriyo,J.,Alves, C. R. , Mato, R. , Avo, A. B. , Saldanha, J. , Almeida, J. S. , Sanches, I. S.和 de Lencastre, H. (2005) J. Clin. Microbiol. 43,1285-1293);來(lái)自腦膜炎萘瑟菌血 清型 B 的外膜囊泡(OMV)制劑(Henrichsen, J. (1995) J. Clin. Microbiol. 33,2759-2762 ; Lau, G. W. , Haataja, S. , Lonetto, Μ. , Kensit, S. Ε. , Marra, Α. , Bryant, Α. P. , McDevitt,
D.,Morrison,D. Α.禾口 Holden,D. W. (2001)Mol. Microbiol. 40,555-571 ;Rosenow,C. ,Ryan, P. , Weiser, J. N. , Johnson, S. , Fontan, P. , Ortqvist, A.禾口 Masure, H. R. (1997)Mol. Microbiol. 25,819-829 ;Tuomanen,E. (1999) Current Opin. Biol. 2,35-39);來(lái)自腦膜炎萘 瑟菌血清型A、B、CW135和/或Y的糖抗原,包括LPS,如來(lái)自血清型C的寡糖(參見(jiàn)PCT/ US99/09346 ;PCT IB98/01665 ;和 PCT IB99/00103);肺炎鏈球菌來(lái)自肺炎鏈球菌的糖或蛋白質(zhì)抗原,尤其是糖,或者PhtD(BVH-ll_2, SP 1003,spr0907) (Adamou 等,Infect. Immun. ,69 :949_53,2001 ;Hamel 等,Infect. Immun. ,72 :2659_70,2004) ;PhtE (BVH-3, SP 1004,spr0908)(Adamou 等,Infect. Immun., 69 949-53,2001 ;Hamel 等,Infect.Immun. ,72 :2659_70,2004) ;PhtB (PhpA, BVH-11, SP1174,sprl060) (Adamou 等,Infect. Immun. ,69 :949_53,2001 ;Zhang 等,Infect. Immun., 69 3827-36,2001 ;Hamel 等,Infect. Immun. ,72 :2659_70,2004) ;PhtA(BVH-11-3, SP1175, sprl061) (Adamou 等,Infect. Immun. ,69 :949_53,2001 ;Wizemann 等,Infect. Immun. ,69 1593-98,2001 ;Zhang 等,Infect. Immun. ,69 :3827_36,2001 ;Hamel 等,Infect. Immun., 72 2659-70,2004) ;NanA(SP1693, sprl536) (Tong 等,Infect.Immun. ,73 :7775_78,2005); SP1872(sprl687)(Brown 等,Infect. Immun. ,69 :6702_06,2001) ;PspC(CbpA, SP2190, sprl995)(Ogunniyi 等,Infect.Immun. ,69 5997-6003,2001) ;PspA(SP0177, spr0121,sprl274) (Briles 等,疫苗,19 :S87-S95, 2001) ;SP0498 (spr0440) ;LytB (SP0965, spr0867) (Wizemann 等,Infect. Immun. ,69 :1593-98,2001) ;AliB (SP1527, sprl382) ;PpmA(SP0981, spr0884)(Overweg 等,Infect. Immun. ,68 :4180_4188,2000) ;LytC(SP1573, sprl431) (Wizemann 等,Infect. Immun. ,69 :1593_98,2001) ;PsaA (Briles 等,Vaccine,19 :S87_S95, 2001) ;PdB (Ogunniyi 等,Infect. Immun. ,69 :5997_6003,2001) ;RPhp (Zhang 等,Infect. Immun. ,69 :3827_36,2001) ;PiuA (Jomaa 等,Vaccine, 24 :5133_39,2006) ;PiaA (Jomaa 等, Vaccine, 24 :5133_39,2006) ;6P⑶(Daniely 等,Clin. Exp. Immunol.,144 :254_263,2006); 或 PppA(Green 等,Infect. Immun. ,73 =981-89,2005)的蛋白質(zhì)或抗原性肽;無(wú)乳鏈球菌(Str印tococcus agalactiae)如B型鏈球菌抗原;釀膿鏈球菌(Str印tococcus pyogenes)如A型鏈球菌抗原;獎(jiǎng)腸球菌(Enterococcus faecalis)或屎腸球菌(Enterococcus faecium)如美 國(guó)專(zhuān)利6,756,361中提供的三糖重復(fù)單元或其他腸球菌衍生抗原;幽門(mén)螺旋桿菌(Helicobacterpylori)包括 Cag、Vac、Nap、HopX、HopY 和 / 或脲 酶抗原;百日咳博德特菌(Bordetella pertussis)如百日咳博德特菌的百日咳全毒素 (PT)和絲狀血凝素(FHA),任選也可以與百日咳桿菌黏附素(pertactin)和/或凝集原2 和3抗原聯(lián)用;金黃色葡萄球菌(Staphylococcus aureus)包括金黃色葡萄球菌5型和8型莢 膜多糖,任選地偶聯(lián)有無(wú)毒性重組綠膿假單胞菌(Pseudomonas aeruginosa)外毒素A如 StaphVAX 、或源自表面蛋白的抗原,侵襲素(殺白細(xì)胞素、激酶、透明質(zhì)酸酶)、抑制吞噬細(xì) 胞吞噬的表面因子(莢膜、蛋白質(zhì)A)、類(lèi)胡蘿卜素、產(chǎn)生過(guò)氧化氫酶、蛋白質(zhì)A、凝固酶、凝血 因子、和/或任選地脫毒的裂解真核細(xì)胞膜的膜破壞性毒素(溶血素、白細(xì)胞毒素、殺白細(xì) 胞素);表皮葡萄球菌(Staphylococcus epidermis)尤其是表皮葡萄球菌粘菌相關(guān)抗原 (SAA);腐生性葡萄球菌(Staphylococcus saprophyticus)(導(dǎo)致尿路感染)尤其是腐 生性葡萄球菌抗原的160kDa血凝素;綠膿假單胞菌(Pseudomonas aeruginosa)尤其是內(nèi)毒素A,Wzz蛋白,綠膿假單 胞菌LPS,更具體是從PA01 (05血清型)分離的LPS,和/或外膜蛋白,包括外膜蛋白F (OprF) (Infectlmmun. 2001 年 5 月;69 (5) :3510_3515);炭疽桿菌(Bacillus anthracis)(炭疽)例如來(lái)自A_組分(致死因子(LF)和 水腫因子(EF))的炭疽桿菌抗原(任選地脫毒),它們具有相同的稱(chēng)為保護(hù)性抗原(PA)的 B-組分;粘膜炎莫拉菌(Moraxella catarrhal is)(呼吸道)包括外膜蛋白抗原 (HMW-0MP),C-抗原,和 / 或 LPS ;鼠疫耶爾森菌(Yersiniapestis)(鼠疫)如 F 1 莢膜抗原(Infect Immun. 2003 年1 月;71(1)) 374-383, LPS (Infect Immun. 1999 年 10 月;67 (10) :5395),鼠疫耶爾森菌 V 抗原(Infect Immun. 1997 年 11 月;65(11) 4476-4482);小腸結(jié)腸炎耶爾森菌(Yersinia enterocolitica)(胃腸病原體)尤其是LPS(InfectImmun. 2002 年 8 月;70 (8) 4414);假結(jié)核耶爾森菌(Yersiniapseudotuberculosis)胃腸病原體抗原;結(jié)核分枝桿菌(Mycobacterium tuberculosis)例如任選地制備成陽(yáng)離子脂 質(zhì)囊泡的脂蛋白、LPS、BCG抗原、抗原85B (Ag85B)的融合蛋白和/或ESAT-6 (Infect Immim. 2004年10月;72 (10) :6148),結(jié)核分枝桿菌(Mtb)異檸檬酸脫氫酶相關(guān)抗原 (Proc. NatlAcadSci U. S. A. 2004 年 8 月 24 日;101 (34) 12652),禾P / 或 MPT51 抗原 (Infectlmmun. 2004 年 7 月;72 (7) 3829);嗜肺軍團(tuán)菌(Legionella pneumophila)(軍團(tuán)病)嗜肺軍團(tuán)菌抗原-任選地源 自asd基因被破壞的細(xì)胞系(Infect Immun. 1998年5月;66(5) 1898);立克次氏體(Rickettsia)包括外膜蛋白,包括外膜蛋白A和/或B (OmpB) (Biochim Biophys Acta. 2004 年 11 月 1 ;1702 (2) :145),LPS 和表面蛋白抗原(SPA) (J Auto immun. 1989 年 6 月;2 增補(bǔ)81);大腸桿菌(E.coli)包括來(lái)自腸毒性大腸桿菌(ETEC)、腸聚集性大腸桿菌 (EAggEC)、彌散粘附性大腸桿菌(DAEC)、腸道致病性大腸桿菌(EPEC)和/或腸出血性大腸 桿菌(EHEC)的抗原;霍亂弧菌(Vibrio cholerae)包括蛋白酶抗原、LPS,尤其是霍亂弧菌II的脂多 糖、Ollnaba 0-特異性多糖、霍亂弧菌0139、IEM108疫苗的抗原(Infect Immun. 2003年10 月;71 (10) :5498-504),和/或閉鎖小帶毒素(Zot);傷寒沙門(mén)菌(Salmonella typhi)(傷寒)包括莢膜多糖,優(yōu)選偶聯(lián)物(Vi,即 vax-TyVi);鼠傷寒沙門(mén)菌(Salmonellatyphimurium)(胃腸炎)考慮將由其衍生的抗原用于 微生物和癌癥治療,包括抑制血管新生和調(diào)節(jié)Ilk ;單核細(xì)胞增多性李斯特菌(Listeria monocytogenes)(免疫缺陷或老年患者中發(fā) 生的全身感染,胎兒感染)源自單核細(xì)胞增多性李斯特菌昀抗原優(yōu)選用作本文所述偶聯(lián) 物/相關(guān)組合物胞質(zhì)內(nèi)遞送的載體;牙齦卟啉單胞菌(Porphyromonas gingivalis)例如牙齦卟啉單胞菌外膜蛋白 (0MP);破傷風(fēng)(Tetanus)如破傷風(fēng)類(lèi)毒素(TT)抗原,例如用作與本文所述組合物偶聯(lián) 的載體蛋白;白喉(Diphtheria):如白喉類(lèi)毒素或白喉類(lèi)毒素突變體,例如CRM197,考慮能夠調(diào) 節(jié)、抑制ADP核糖基化或與其相關(guān)的其他抗原與本文所述組合物聯(lián)用/共同給藥/偶聯(lián),白 喉類(lèi)毒素可用作載體蛋白;伯氏疏螺旋體(Borrelia burgdorferi)(萊姆病)如P39和P13的相關(guān)抗原(一 種整體膜蛋白,Infect Immun. 2001 年5月;69(5) :3323_3334),VlsE抗原變異蛋白(J. Clin Microbiol.1999 年 12 月;37(12) 3997);乙型流感嗜血桿菌(Haemophilus influenzae B)例如由其衍生的糖抗原;克雷伯桿菌(Klebsiella)如0MP,包括0MP A,或任選地與破傷風(fēng)類(lèi)毒素偶聯(lián)的 多糖;淋病奈瑟菌(Neiserria gonorrhoeae)包括Por (或孔蛋白)蛋白,如PorB(參
32見(jiàn) Zhu 等,Vaccine (2004) 22 660-669),轉(zhuǎn)移結(jié)合蛋白,如 TbpA 和 TbpB(參見(jiàn) Price 等, Infection andlmmunity (2004) 71 (1) :277_283),不透明性蛋白(如 Opa),還原可修飾 蛋白(Rmp)和外膜囊泡(0MV)制劑(參見(jiàn) Plante 等,JInfectious Disease (2000) 182 848-855),也可參見(jiàn)例如,W099/24578, W099/36544, W099/57280, W002/079243);肺炎衣原體(Chlamydiapneumoniae)尤其是肺炎衣原體蛋白質(zhì)抗原;沙眼衣原體(Chlamydia trachomatis)包括源自血清型A、B、Ba和C的抗原(沙 眼病原體,失明原因之一),源自血清型U、L2和L3 (與性病淋巴肉芽腫相關(guān))的抗原和源自 血清型D-K的抗原;蒼白密螺旋體(Tr印onema pallidum)(梅毒)尤其是TmpA抗原;和杜氏嗜血桿菌(Haemophilus ducreyi)(引起軟下疳)包括外膜蛋白(DsrA)。雖然未具體提及,但本文所述的其它細(xì)菌抗原可以是上述任何一種細(xì)菌的莢膜抗 原、多糖抗原或蛋白質(zhì)抗原。其它細(xì)菌抗原也可包括外膜囊泡(0MV)制劑。此外,抗原包括 活、減毒、裂解(對(duì)于有包膜的病毒而言)和/或純化的任何上述細(xì)菌。本文所述細(xì)菌或微 生物來(lái)源的抗原可以是革蘭氏陰性菌或革蘭氏陽(yáng)性菌,以及需氧或厭氧菌。此外,任何上述細(xì)菌來(lái)源的糖(多糖、LPS、L0S或寡糖)可偶聯(lián)于另一種試劑 或抗原,例如載體蛋白(例如crm197)。這種偶聯(lián)可以是糖上羰基部分與蛋白質(zhì)氨基基 團(tuán)還原胺化實(shí)現(xiàn)的直接偶聯(lián),如美國(guó)專(zhuān)利5,360,897和Can J Biochem CellBiol. 1984 年5月;62(5) :270-5所述?;蛘?,糖可以通過(guò)連接基團(tuán)偶聯(lián),例如采用《生物偶聯(lián)技 術(shù)》(Bioconjugate Techniques),1996和CRC,《蛋白質(zhì)偶聯(lián)與交聯(lián)化學(xué)》(Chemistry of Protein Conjugation and Cross-Linking),1993中提供的琥珀酰胺或其他連接鍵進(jìn)行偶 聯(lián)。病毒抗原流感病毒包括全病毒顆粒(減毒)、裂解部分或含有血凝素(HA)和/或神經(jīng)氨 酸酶(NA)表面蛋白的亞單位,流感抗原可源自雞胚或基于細(xì)胞培養(yǎng)繁殖,和/或流感抗原 可源自甲、乙和/或丙型流感及其他流感;呼吸道合胞病毒(RSV)包括RSV A2毒株的F蛋白(J Gen Virol. 2004年11月; 85 (Pt 11) 3229)和 / 或 G 糖蛋白;副流感病毒(PIV)包括1、2和3型PIV,優(yōu)選含有血凝素、神經(jīng)氨酸酶和/或融合 糖蛋白;脊髓灰質(zhì)炎病毒包括源自小核糖核酸病毒科(picornaviridae)的抗原,優(yōu)選脊 髓灰質(zhì)炎病毒抗原如0PV,或優(yōu)選IPV ;麻疹病毒包括任選地與Protollin組合的裂解麻疹病毒(MV)抗原,和/或匪R 疫苗中包含的抗原;腮腺炎病毒包括MMR疫苗中包含的抗原;風(fēng)疹病毒包括MMR疫苗中包含的抗原以及來(lái)自披蓋病毒科(Togaviridae)的其 他抗原,包括登革熱病毒;狂犬病病毒例如凍干的滅活病毒(RabAvert );黃病毒科(Flaviridae)病毒例如黃熱病病毒、日本腦炎病毒、登革熱病毒(1、2、 3或4型)、蜱媒腦炎病毒和西尼羅病毒(以及由其衍生的抗原);
杯狀病毒科(Calici viridae)由其衍生的抗原;HIV 包括 HIV-1 或 HIV-2 毒株抗原,例如 gag(p24gag 和 p55gag)、env(gpl60 和 gp41)、pol、tat、nef、rev vpu、微小蛋白(miniprotein)(優(yōu)選 p55gag 禾口 gpl40v 缺失)禾口 來(lái)自分離物 HIVmpHIVsmHIVupHIV^^HIV^HIV-lmpHIV-luwHIV-2 的抗原;猴免疫缺 陷病毒(SIV)及其他;輪狀病毒包括乂卩4、乂卩5、乂卩6、乂卩7、乂卩8蛋白(ProteinExpr Purif. 2004 年 12 月; 38(2) 205)和 / 或 NSP4 ;瘟病毒例如來(lái)自經(jīng)典的豬熱病毒、牛病毒性腹瀉病毒和/或邊界病病毒的抗原。細(xì)小病毒例如細(xì)小病毒B19 ;冠狀病毒包括SARS病毒抗原,尤其是突起蛋白或由其衍生的蛋白酶,以及TO 04/92360中包括的抗原;甲型肝炎病毒例如滅活病毒;乙型肝炎病毒例如表面和/或核心抗原(sAg),以及前表面序列前-S1和 前-S2 (過(guò)去稱(chēng)為前-S),以及上述物質(zhì)的組合,例如sAg/前-Sl、sAg/前-S2、sAg/前-S1/ 前-S2和前-S1/前-S2(例如參見(jiàn)AHBV疫苗人用疫苗與疫苗接種(AHBV Vaccines-Human Vaccines and Vaccination),第 159-176 頁(yè);和美國(guó)專(zhuān)利 4,722,840、5,098,704、 5,324,513 ;Beames 等,J. Virol. (1995)69 :6833_6838,Birnbaum 等,J. Virol. (1990)64 3319-3330 ;和 Zhou 等,J. Virol. (1991)65 :5457_5464);丙型肝炎病毒例如El、E2、El/E2(參見(jiàn) Houghton 等,Hepatology(1991) 14 381)、NS345多聚蛋白、NS 345-核心多聚蛋白、核心和/或來(lái)自非結(jié)構(gòu)區(qū)的肽(國(guó)際公開(kāi) W0 89/04669,W0 90/11089 和 W0 90/14436);丁型肝炎病毒(HDV)由其衍生的抗原,尤其是源自HDV的S -抗原(參見(jiàn)例如, 美國(guó)專(zhuān)利5,378,814);戊型肝炎病霉(HRV)由其衍生的抗原;庚型肝炎病毒(HGV)由其衍生的抗原;水痘-帶狀皰疹病毒由水痘-帶狀皰疹病毒衍生的抗原(VZV) (J. Gen. Virol. (1986)67 1759);EB 病毒由 EBV 衍生的抗原(Baer 等,Nature (1984) 310 207);巨細(xì)胞病毒CMV抗原,包括gB和gH(巨細(xì)胞病毒(J. K. McDougall編, Springer-Verlag 1990)第 125-169 頁(yè));單純皰疹病毒包括由HSV-1或HSV-2毒株衍生的抗原,以及糖蛋白gB、gD和 gH(McGeoch 等,J. Gen. Virol. (1988)69 1531 和美國(guó)專(zhuān)利 5,171,568);人皰疹病毒由其他人皰疹病毒如HHV6和HHV7衍生的抗原;和HPV 包括與人乳頭狀瘤病毒(HPV)相關(guān)或由其衍生的抗原,例如E1_E7、L1、L2以 及它們的融合形式中的一種或多種,具體說(shuō)本文所述組合物可包含含有L1主要衣殼蛋白 的病毒樣顆粒作1^),更具體說(shuō)朋乂抗原是針對(duì)朋乂血清型6、11、16和/或18中的一種或 多種具有保護(hù)性的。還提供了在《病毒》(Vaccines),第4版(Plotkin和Orenstein編,2004);《醫(yī)學(xué) 微生物學(xué)》(Medical Microbiology)第 4 版(Murray 等編,2002);《病毒學(xué)》(Virology),第3 版(ff. K. Joklik 編,1988);《基礎(chǔ)病毒學(xué)》(Fundamental Virology),第 2 版(B. N. Fields 和D.M.Knipe,編,1991)中包含的抗原、組合物、方法和微生物,考慮將它們與本文所述組 合物聯(lián)用。此外,抗原包括活、減毒、裂解和/或純化的任何上述病毒。真菌抗原與疫苗聯(lián)合使用的真菌抗原包括美國(guó)專(zhuān)利4,229,434和4,368,191中所述 的抗原,用于預(yù)防和治療須癬毛癬菌(Trichophyton mentagrophyte)導(dǎo)致的毛癬菌病 (trichopytosis);美國(guó)專(zhuān)利5,277,904和5,284,652中所述的用于預(yù)防動(dòng)物皮膚癬菌感 染的廣譜皮膚癬菌疫苗的抗原,所述動(dòng)物例如是豚鼠、貓、兔、馬和羊,這些抗原包含有效量 的殺傷性馬毛癬菌(T. equinum)、須癬毛癬菌(T. mentagrophytes)(顆粒變種)、犬小孢 子菌(M. canis)和/或石膏樣小孢子菌(M. gypseum)的懸浮液,任選地含有佐劑;美國(guó)專(zhuān) 利5,453,273和6,132,733中所述的用于癬菌病疫苗的抗原,其在載體中包含有效量的經(jīng) 勻漿化處理的甲醛殺傷的真菌,即犬小孢子菌培養(yǎng)物;以及美國(guó)專(zhuān)利5,948,413中所述的 抗原,涉及腐皮病(pythiosis)的胞外和胞內(nèi)蛋白質(zhì)。抗真菌疫苗中鑒定的其他抗原包括 Ringvac bovisLTF-130 禾口 Bioveta。并且,這里所用的真菌抗原可衍生自皮膚癬菌,包括絮狀表皮霉菌 (Epidermophyton f loccusum)、奧杜安氏小抱子菌(Microsporum audouini)、犬小 孢子菌(Microsporum canis)、扭曲小孢子菌(Microsporum distortum)、馬小孢 子菌(Microsporum equinum)、石膏樣小抱子菌(Microsporum gypsum)、矮小小抱 子菌(Microsporum nanum)、同心性毛癬菌(Trichophyton concentricum)、馬毛 M M (Trichophyton equinum)、 _ € _ 胃(Trichophyton gallinae)、^* # # € _ 菌(Trichophyton gypseum)、蒙氏毛癬菌(Trichophyton megnini)、須癬毛癬菌 (Trichophyton mentagrophytes)、發(fā)瘤毛瘤菌(Trichophyton quinckeanum)、紅色毛 M M (Trichophyton rubrum)、胃 g € _ 胃(Trichophyton schoenleini)、 ■ 1 € _ 菌(Trichophyton tonsurans)、撫狀毛癬菌(Trichophyton verrucosum),撫狀毛癬菌 (T. verrucosum)白色變種(album)、盤(pán)狀變種(discoides)、赭色變種(ochraceum),紫色毛 瘤菌(Trichophyton violaceum)禾口 / 或蜜塊狀毛瘤菌(Trichophyton faviforme)。與本文所述組合物聯(lián)用的用作抗原或衍生抗原的真菌病原體包括煙曲霉 (Aspergillus fumigatus)、黃曲霉(Aspergillusflavus)、黑曲霉(Aspergillusniger)、 構(gòu)巢曲霉(Aspergillus nidulans)、 土曲霉(Aspergillus terreus)、聚多曲霉 (Aspergillussydowi)> 黃曲霉(Aspergillus flavatus)> 灰綠曲霉(Aspergillus glaucus)、頭狀芽裂殖菌(Blastoschizomyces capitatus)、白假絲酵母(Candida albicans)、(Candida enolase)、熱帶假絲酵母(Candida tropicalis)、光滑假絲酵母 (Candida glabrata)、克魯斯假絲酵母(Candida krusei)、近平滑假絲酵母(Candida parapsilosis)、類(lèi)星形假絲酵母(Candidastellatoidea)、克魯斯假絲酵母(Candida kusei)、(Candidaparakwsei)、葡萄牙假絲酵母(Candida lusitaniae)、偽熱帶假絲 酵母(Candidapseudotropicalis)、季也蒙假絲酵母(Candida guilliermondi)、卡氏 枝?包霉(Cladosporium carrionii)、粗球抱子菌(Coccidioides immitis)、皮炎芽 生菌(Blastomyces dermatidis)、新型隱球菌(Cryptococcus neoformans)、棒地霉(Geotrichum clavatum)、莢膜組織胞楽菌(Histoplasma capsulatum)、巴西副球孢子菌 (Paracoccidioides brasiliensis)、卡氏月市抱子蟲(chóng)(Pneumocystis carinii)、詭譎腐霉 (Pythiumn insidiosum)、皮屑芽胞菌(Pityrosporum ovale)、酉良酒酵母(Sacharomyces cerevisae)、布拉酵母(Saccharomycesboulardii)、粟酒酵母(Saccharomyces pombe)、尖 端賽多抱子菌(Scedosporiumapiosperum)、申克抱子絲菌(Sporothrix schenckii)、白吉 利絲孢酵母(Trichosporonbeigelii)、馬爾尼菲青霉菌(Penicillium marneffei)、馬拉 色菌(Malassezia spp.)、著色真菌(Fonsecaea spp.)、王氏霉菌(Wangiella spp.)、抱子 絲菌(Sporothrix spp.)、魅獎(jiǎng)霉(Basidiobolus spp.)、耳霉(Conidiobolus spp.)、根 霉(Rhizopus spp.)、毛霉(Mucor spp.)、犁頭霉(Absidia spp.)、被抱霉(Mortierella spp.)、小克銀漢霉(Cunninghamella spp.)禾口瓶霉(Saksenaea spp.)。衍生得到抗原的其他真菌包括支鏈孢屬(Alternaria spp)、彎孢屬 (Curvulariaspp)、長(zhǎng)螺抱屬(Helminthosporium spp)、德抱菌屬(Fusarium spp)、曲 霉(Aspergillusspp)、青霉菌(Penicillium spp)、單線屬(Monolinia spp)、絲核菌屬 (Rhizoctonia spp)、擬青毒屬(Paecilomyces spp)、半知菌綱毒菌(Pithomyces spp)禾口分 支抱子菌屬(Cladosporium spp)。本領(lǐng)域熟知產(chǎn)生真菌抗原的方法(參見(jiàn)美國(guó)專(zhuān)利6,333,164)。在一些方法中,從 已基本除去或至少部分除去細(xì)胞壁的真菌細(xì)胞的不溶性組分中提取和分離溶解組分,其特 征在于所述方法包括獲得活真菌細(xì)胞;獲得已基本除去或至少部分除去細(xì)胞壁的真菌細(xì) 胞;破碎已基本除去或至少部分除去細(xì)胞壁的真菌細(xì)胞;獲得不溶性組分;以及從不溶性 組分中提取和分離溶解組分。STD 抗原在一些實(shí)施方式中,本發(fā)明組合物和方法能夠?qū)沟奈⑸?細(xì)菌、病毒和/或真 菌)包括導(dǎo)致性傳播疾病(STD)的微生物和/或在其表面上展示可能成為本文所述靶點(diǎn)或 抗原組合物的抗原的那些微生物。在一些實(shí)施方式中,組合物與源自病毒性或細(xì)菌性STD 的抗原組合。源自細(xì)菌或病毒的抗原可以與本文所述組合物聯(lián)合給予,以提供針對(duì)至少一 種以下STD的保護(hù)作用衣原體、生殖器皰疹、肝炎(特別是HCV)、生殖器疣、淋病、梅毒和/ 或軟下疳(參見(jiàn)W000/15255)。在一些實(shí)施方式中,本文所述組合物與用于預(yù)防或治療STD的一種或多種抗原共 同給予。優(yōu)選源自以下STD相關(guān)病毒的抗原與本文所述組合物共同給予肝炎(特別是 HCV)、HPV、HIV或HSV (詳述見(jiàn)上文)。此外,優(yōu)選源自以下STD相關(guān)細(xì)菌的抗原與本文所述組合物共同給予,它們是淋 病奈瑟菌、肺炎衣原體、沙眼衣原體、蒼白密螺旋體或杜氏嗜血桿菌(詳述見(jiàn)上文)。呼吸道抗原肺炎鏈球菌抗原可以是呼吸道抗原,可進(jìn)一步用于預(yù)防和/或治療呼吸道病原體 感染的方法所用的免疫原性組合物中,所述病原體包括病毒、細(xì)菌或真菌,例如呼吸道合胞 病毒(RSV)、PIV、SARS病毒、流感病毒、炭疽桿菌,具體是通過(guò)減輕或防止感染和/或呼吸道 病毒感染的一種或多種癥狀。包含本文所述抗原,例如源自呼吸道病毒、細(xì)菌或真菌的抗原 的組合物可與本文所述組合物聯(lián)用,給予處于接觸特定呼吸道微生物的風(fēng)險(xiǎn)中、已接觸呼吸道微生物或者受到呼吸道病毒、細(xì)菌或真菌感染的個(gè)體。本文所述組合物可以與一種或 多種呼吸道病原體的抗原同時(shí)或在同一制劑中并行給予。給予組合物導(dǎo)致呼吸道感染的一 種或多種癥狀的發(fā)生率和/或嚴(yán)重性降低。兒科/老年病學(xué)抗原在一些實(shí)施方式中,本文所述組合物與用于治療兒科群體的一種或多種抗原如兒 科抗原聯(lián)用。在一些實(shí)施方式中,兒科群體中的對(duì)象年齡小于約3歲,或小于約2歲,或小 于約1歲。在一些實(shí)施方式中,兒科抗原(與本文所述組合物聯(lián)用)在至少1、2或3年內(nèi) 分多次給予。在一些實(shí)施方式中,本文所述組合物與用于治療老年病學(xué)群體的一種或多種抗原 如老年病學(xué)抗原聯(lián)用。在一些實(shí)施方式中,老年病學(xué)群體中的對(duì)象年齡大于約50歲,大于 約55歲,大于約60歲,大于約65歲,大于約70歲,大于約75歲,大于約80歲,或大于約85 歲。在一些實(shí)施方式中,老年病學(xué)抗原(與本文所述組合物聯(lián)用)在至少1、2或3年內(nèi)分 多次給予。其他抗原可與本發(fā)明組合物聯(lián)用的其他抗原包括醫(yī)院獲得性(醫(yī)源性)相關(guān)抗原。在一些實(shí)施方式中,考慮將寄生性抗原與本文所述組合物聯(lián)用。寄生性抗原的例 子包括那些源自導(dǎo)致瘧疾和/或萊姆病的生物體的抗原。在一些實(shí)施方式中,與本文所述組合物聯(lián)用的抗原與蚊媒病有關(guān)或能有效對(duì)抗蚊 媒病。在一些實(shí)施方式中,與本文所述組合物聯(lián)用的抗原與腦炎有關(guān)或能有效對(duì)抗腦炎。在 一些實(shí)施方式中,與本文所述組合物聯(lián)用的抗原與神經(jīng)系統(tǒng)感染有關(guān)或能有效對(duì)抗神經(jīng)系 統(tǒng)感染。在一些實(shí)施方式中,與本文所述組合物聯(lián)用的抗原是可通過(guò)血液或體液傳播的抗原??乖苿┰谝恍┓矫?,提供了吸附抗原的微粒的制備方法。該方法包括(a)通過(guò)分散含有 (i)水、(ii)去污劑、(iii)有機(jī)溶劑和(iv)可生物降解聚合物的混合物提供乳液,所述可 生物降解聚合物選自聚(a-羥酸)、聚羥基丁酸、聚己內(nèi)酯、聚原酸酯、聚酐和聚腈基丙烯 酸酯。相對(duì)于有機(jī)溶劑,該聚合物在混合物中的濃度一般約為_(kāi)30%,而混合物中去污 劑-聚合物的重量比一般約為0.00001 1-0.1 1(更一般約為0.0001 1-0.1 1,約 為0.001 1-0.1 1,或約為0.005 1-0.1 1) ;(b)除去乳液中的有機(jī)溶劑;和(c) 使抗原吸附于微粒表面上。在一些實(shí)施方式中,相對(duì)于有機(jī)溶劑,可生物降解聚合物的濃度 約為 3% -10%。在一些實(shí)施方式中,這里使用的微粒由可滅菌、無(wú)毒并且可生物降解的材料制成。 這些材料包括但不限于聚(a-羥酸)、聚羥基丁酸、聚己內(nèi)酯、聚原酸酯、聚酐、PACA和聚 氰基丙烯酸酯。在一些實(shí)施方式中,本文所述方法中使用的微粒衍生自聚(a -羥酸),具體 說(shuō),衍生自聚(丙交酯)("PLA")或D,L-丙交酯和乙交酯或乙醇酸的共聚物,如聚(D, L-丙交酯-乙交酯共聚物)(〃 PLG"或"PLGA"),或D,L-丙交酯和己內(nèi)酯的共聚物。該 微??裳苌跃哂懈鞣N分子量的各種聚合物原料,在共聚物如各種丙交酯乙交酯比例的 PLG情況下,選擇丙交酯乙交酯比例是主要問(wèn)題,部分取決于共同給予的大分子。下面更全面地討論這些參數(shù)。其它細(xì)菌抗原也可包括外膜囊泡(0MV)制劑??乖部晌皆诟鞣N革蘭氏陽(yáng)性菌的肽聚糖上,形成革蘭氏陽(yáng)性增強(qiáng)子基質(zhì) (GEM)顆粒,如 Bosma 等 Appl.Env. Microbiol. ,72 :880_889,2006 所述,其全部?jī)?nèi)容被納入 本文作為參考。該方法依賴于LysM基序(Buist等,J. Bact.,177 1554-63,1995 ;Bateman 和Bycroft,J. Mol. Biol.,299 :1113_19,2000)與酸處理細(xì)胞的細(xì)胞壁肽聚糖的非共價(jià)結(jié) 合。簡(jiǎn)言之,將連接于一個(gè)或多個(gè)LysM基序(例如,非共價(jià)或共價(jià)連接(例如,以融合蛋 白形式或者通過(guò)偶聯(lián)連接))的多肽抗原加入酸處理的革蘭氏陽(yáng)性菌中??乖囊愿哂H 和力結(jié)合,可用于免疫原性組合物中。這些方法中使用的酸的例子包括三氯乙酸(例如, 0.1%-10%)、乙酸(例如5. 6M)、HC1 (例如0.01M)、乳酸(例如0. 72M)和甲酸(例如 0. 56M)。美國(guó)專(zhuān)利6,884,435中提供了其它制備方法和抗原(尤其是腫瘤抗原)??乖瓍⒖嘉墨I(xiàn) 以下參考文獻(xiàn)包括與本文所述組合物聯(lián)用的抗原,它們各自的內(nèi)容具體納入本文 作為參考國(guó)際專(zhuān)利申請(qǐng)W099/24578國(guó)際專(zhuān)利申請(qǐng)W099/36544國(guó)際專(zhuān)利申請(qǐng)W099/57280國(guó)際專(zhuān)利申請(qǐng)W000/22430Tettelin 等(2000) Science 287:1809-1815國(guó)際專(zhuān)利申請(qǐng)W096/29412Pizza 等(2000) Science 287:1816-1820.PCT W0 01/52885.Bjune 等(1991) Lancet 338(8775).Fuskasawa 等(1999) Vaccine 17:2951—2958.Rosenqist 等(1998)Dev. Biol. Strand 92 :323_333.Costantino 等(1992) Vaccine 10:691-698.Costantino 等(1999) Vaccine 17:1251—1263.Watson(2000)Pediatr Infect Dis J 19:331-332.Rubin(20000)Pediatr Clin North Am 47 =269-285, v.Jedrzejas(2001)Microbiol Mol Biol Rev 65:187—207.要求GB0016363. 4 ;W0 02/02606 ;PCT IB/01/00166 的優(yōu)先權(quán)的 2001 年 7 月 3 日
提交的國(guó)際專(zhuān)利申請(qǐng)Kalman 等(1999)Nature Genetics 21 :385_389.Read 等(2000)Nucleic Acids Res 28 :1397-406.Shirai 等(2000) J. Infect. Dis 181 (增補(bǔ) 3) :S524_S527.國(guó)際專(zhuān)利申請(qǐng)W099/27105.國(guó)際專(zhuān)利申請(qǐng)W000/27994.國(guó)際專(zhuān)利申請(qǐng)W000/37494.
國(guó)際專(zhuān)利申請(qǐng)W099/28475.Bell (2000)Pediatr Infect Dis J19 :1187_1188.Iwarson(1995)APMIS 103:321-326.Gerlich 等(1990) Vaccine 8 增補(bǔ):S63_68 和 79-80.Hsu 等(1999)Clin Liver Dis 3:901-915. Gastofsson 等(1996) N. Engl. J. Med. 334- :349_355.Rappuoli 等(1991)TIBTECH 9 :232_238.《疫苗》(Vaccines)(1988)編 Plotkin 和 Mortimer. ISBN 0-7216-1946-0.Del Guidice 等(1998)Molecular Aspects of Medicine 19 :1_70.國(guó)際專(zhuān)利申請(qǐng)W093/018150.國(guó)際專(zhuān)利申請(qǐng)W099/53310.國(guó)際專(zhuān)利申請(qǐng)W098/04702.Ross 等(2001) Vaccine 19:135-142.Sutter 等(2000)Pediatr Clin North Am 47 :287_308.Zimmerman 禾口 Spann(1999)Am Fan Physician 59 :113—118,125—126.Dreensen (1997) Vaccine 15±|#”S2_6.MMWR Morb Mortal ffkly r印 1998 年 1 月 16 日47(1) :12,9.McMichael (2000) Vaccinel9 增補(bǔ) 1 :S101_107.Schuchat(1999)Lancet 353(9146) :51_6.GB 專(zhuān)利申請(qǐng) 0026333. 5,0028727. 6 和 0105640. 7.Dale(1999)Infect Disclin North Am 13 :227_43,viii.Ferretti 等(2001)PNAS USA 98 4658-4663.Kuroda 等(2001) Lancet 357(9264) :1225_1240 ;也可參見(jiàn) 1218-1219.Ramsay 等(2001)Lancet 357(9251) :195-196.Lindberg(1999) Vaccine 17 增補(bǔ) 2 :S28_36.Buttery 禾口 Moxon (2000) J R Coil Physicians Long 34:163—168.Ahmad 和 Chapnick(1999) Infect Dis Clin North Am 13 :113_133,vii.Goldblatt (1998) J. Med. Microbiol. 47 :663_567.歐洲專(zhuān)利0477508.美國(guó)專(zhuān)利5,306,492.國(guó)際專(zhuān)利申請(qǐng)W098/42721.《偶聯(lián)疫苗》(ConjugateVaccines) (Cruse 等編)ISBN 3805549326,具體是第 10 卷48-114.Hermanson(1996)《生物偶聯(lián)技術(shù)》(Bioconjugate Techniques) ISBN 012323368 和 012342335X.歐洲專(zhuān)利申請(qǐng)0372501.歐洲專(zhuān)利申請(qǐng)0378881.歐洲專(zhuān)利申請(qǐng)0427347.國(guó)際專(zhuān)利申請(qǐng)W093/17712.
39
國(guó)際專(zhuān)利申請(qǐng)W098/58668.歐洲專(zhuān)利申請(qǐng)0471177.國(guó)際專(zhuān)利申請(qǐng)W000/56360.國(guó)際專(zhuān)利申請(qǐng)W000/67161.融合蛋白本文所述組合物中使用的肺炎鏈球菌多肽可以作為獨(dú)立多肽存在于組合物中,但 在一些實(shí)施方式中,至少兩種(即 2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17 或 18 種) 抗原可以表達(dá)成一條多肽鏈(“雜交”或“融合”多肽)。這種融合多肽具有以下兩方面的 主要優(yōu)點(diǎn)首先,本身不穩(wěn)定或者表達(dá)較差的多肽可以通過(guò)加入能夠克服該問(wèn)題的合適的 融合伴侶得到改善,其次,商業(yè)生產(chǎn)得到簡(jiǎn)化,因?yàn)橹恍枥靡淮伪磉_(dá)和純化即可生產(chǎn)可作 抗原應(yīng)用的兩種多肽。融合多肽可包含一種或多種本文所述肺炎鏈球菌多肽編碼的多肽序列。因此,本 文所述組合物可包含一種融合肽,所述融合肽具有第一氨基酸序列和第二氨基酸序列,所 述第一和第二氨基酸序列選自由肺炎鏈球菌菌毛I(xiàn)I島(INV104B)或其片段所編碼的蛋白 質(zhì)。在一些實(shí)施方式中,所述融合多肽中的第一和第二氨基酸序列包含不同的表位。在一些實(shí)施方式中,優(yōu)選由本文所述肺炎鏈球菌多肽序列編碼的兩種、三種、四 種、五種、六種、七種、八種、九種或十種抗原的氨基酸序列構(gòu)成的雜交體(或融合體)。在一 些實(shí)施方式中,優(yōu)選由本文所述肺炎鏈球菌多肽序列編碼的兩種、三種、四種或五種抗原的 氨基酸序列構(gòu)成的雜交體。不同的雜交多肽可以混合在單一制劑中。在這種組合內(nèi),本文所述肺炎鏈球菌多 肽序列所編碼的序列可以在一種以上的雜交多肽中和/或作為非雜交多肽存在。然而,在 一些實(shí)施方式中,抗原以雜交形式或者非雜交形式存在,但這兩種形式不同時(shí)存在。雜交多肽可以通式NH2-A-{-X-L-}n-B-C00H表示,其中X是本文所述肺炎鏈球菌 多肽或其片段的氨基酸序列;L是任選的接頭氨基酸序列;A是任選的N-末端氨基酸序列; B是任選的C-末端氨基酸序列;n是2、3、4、5、6、7、8、9、10、11、12、13、14或15。如果野生型形式中-X-部分具有前導(dǎo)肽序列,在雜交蛋白中可以包含或者略去其 前導(dǎo)肽。在一些實(shí)施方式中,前導(dǎo)肽可缺失,除非-X-部分位于雜交蛋白的N-末端,即保 留&的前導(dǎo)肽,但略去X2. . . Xn的前導(dǎo)肽。這相當(dāng)于刪除所有前導(dǎo)肽并使用&的前導(dǎo)肽作 為-A-部分。在{-X-L-}的各個(gè)n值的情況下,接頭氨基酸序列-L-可存在或不存在。例 如,當(dāng) n = 2 時(shí),雜交體可以是 NHfXfLfXfl^-COOH、NHfXfXfCOOH、NHfXfLfXfCOOH、 NHfXfX^LfCOOH等。接頭氨基酸序列-L-一般較短(如20個(gè)或更少的氨基酸,即19、18、 17、16、15、14、13、12、11、10、9、8、7、6、5、4、3、2、1個(gè)氨基酸)。例子包括有利于克隆的短肽 序列,多聚甘氨酸接頭(即,包括Glyn,其中n = 2、3、4、5、6、7、8、9、10或更大)。本領(lǐng)域技 術(shù)人員顯然了解其它合適的接頭氨基酸序列。有用的接頭是GSGGGG,Gly-Ser 二肽由BamHI 限制位點(diǎn)形成,因而有助于克隆和操作,(Gly)4四肽是常用的多聚甘氨酸接頭。在上述雜交多肽通式中,-A-是任選的N-末端氨基酸序列。它一般較短(例如,40 個(gè)或更少的氨基酸,即 39、38、37、36、35、34、33、32、31、30、29、28、27、26、25、24、23、22、21、 20、19、18、17、16、15、14、13、12、11、10、9、8、7、6、5、4、3、2、1個(gè)氨基酸)。例子包括指導(dǎo)蛋白質(zhì)運(yùn)輸?shù)那皩?dǎo)序列,或有利于克隆或純化的短肽序列。本領(lǐng)域技術(shù)人員顯然了解其它合適 的N-末端氨基酸序列。如果&缺少其自身的N-末端甲硫氨酸,-A-優(yōu)選是提供N-末端甲 硫氨酸的寡肽(例如,具有1、2、3、4、5、6、7或8個(gè)氨基酸)。在上述雜交多肽通式中,-B-是任選的C末端氨基酸序列。它一般較短(例如,40 個(gè)或更少的氨基酸,即 39、38、37、36、35、34、33、32、31、30、29、28、27、26、25、24、23、22、21、 20、19、18、17、16、15、14、13、12、11、10、9、8、7、6、5、4、3、2、1個(gè)氨基酸)。例子包括指導(dǎo)蛋白 質(zhì)運(yùn)輸?shù)男蛄校欣诳寺』蚣兓亩屉男蛄?,或提高蛋白質(zhì)穩(wěn)定性的序列。本領(lǐng)域技術(shù)人 員顯然了解其它合適的C-末端氨基酸序列。在上述雜交多肽通式中,最優(yōu)選n為2或3。核酸本說(shuō)明書(shū)提供了編碼肺炎鏈球菌多肽序列和/或雜交融合多肽的核酸。本說(shuō)明書(shū) 還提供了編碼肺炎鏈球菌多肽抗原和/或本文所述雜交融合多肽的核酸。并且,本說(shuō)明書(shū) 提供了能夠與這些核酸雜交,優(yōu)選在“高度嚴(yán)謹(jǐn)”條件下(例如,65°C,在0. lx SSC,0.5% SDS溶液中)雜交的核酸。本文所述多肽可通過(guò)多種方式(例如,重組表達(dá)、從細(xì)胞培養(yǎng)物純化、化學(xué)合成 等)并以多種形式(例如,天然、融合、非糖基化、脂化等形式)進(jìn)行制備。它們優(yōu)選制備成 基本純形式(即基本上不含其他宿主細(xì)胞蛋白)。本文所述核酸可以許多方式(例如,通過(guò)化學(xué)合成,來(lái)自基因組或cDNA文庫(kù),來(lái)自 生物體本身等)并以各種形式(例如,單鏈、雙鏈、載體、探針等)進(jìn)行制備。它們優(yōu)選以合 適的純化形式制備(即基本上不含其他宿主細(xì)胞核酸)。本文所用術(shù)語(yǔ)“核酸”包括DNA和RNA,以及它們的類(lèi)似物,例如含有經(jīng)修飾的主鏈 (例如硫代磷酸酯等)的類(lèi)似物,以及肽核酸(PNA)等等。本文所述組合物包含含有上述序 列的互補(bǔ)序列的核酸(例如出于反義和探針目的)。本說(shuō)明書(shū)還揭示了一種多肽制備方法,該方法包括以下步驟在誘導(dǎo)多肽表達(dá)的 條件下培養(yǎng)用本文所述核酸轉(zhuǎn)染的宿主細(xì)胞。本說(shuō)明書(shū)還揭示了一種多肽制備方法,該方法包括通過(guò)化學(xué)方式合成至少一部分 多肽的步驟。本說(shuō)明書(shū)還揭示了一種核酸制備方法,該方法包括用基于引物的擴(kuò)增方法(例如 PCR)擴(kuò)增核酸的步驟。本說(shuō)明書(shū)還揭示了一種核酸制備方法,該方法包括通過(guò)化學(xué)方式合成至少一部分 的核酸的步驟。純化和重組表達(dá)本文所述的肺炎鏈球菌多肽序列可從天然肺炎鏈球菌分離,或者它們可以(例 如)在異源宿主中重組制備。例如,本文所述的肺炎鏈球菌菌毛I(xiàn)I島(INV104B)抗原可以 從含有肺炎鏈球菌菌毛I(xiàn)I島(INV104B)的肺炎鏈球菌分離,或者它們可以(例如)在異源 宿主中重組制備。異源宿主可以是原核(例如細(xì)菌)或真核生物。優(yōu)選大腸桿菌,但也可采用 其他合適的宿主,包括枯草桿菌(Bacillus subtilis)、霍亂弧菌、傷寒沙門(mén)菌、鼠傷寒 沙門(mén)菌、乳糖奈瑟菌(Neisseria lactamica)、灰色奈瑟菌(Neisseria cinerea)、分枝桿菌(Mycobacteria)(例如結(jié)核分枝桿菌)、格氏鏈球菌(S. gordonii)、乳酸乳球菌 (L. lactis)、酵母等。在需要表達(dá)的本文所述的肺炎鏈球菌多肽序列中加入標(biāo)簽蛋白,形成含有標(biāo)簽 蛋白和所述多肽的融合蛋白,以便于多肽的重組制備。例如,在需要表達(dá)的肺炎鏈球菌菌 毛I(xiàn)I島(INV104B)菌毛抗原中加入標(biāo)簽蛋白,形成含有標(biāo)簽蛋白和肺炎鏈球菌菌毛I(xiàn)I 島(INV104B)菌毛抗原的融合蛋白,以便于多肽的重組制備。這種標(biāo)簽蛋白有利于表達(dá) 的蛋白質(zhì)的純化、檢測(cè)和穩(wěn)定。適用于本文所述組合物的標(biāo)簽蛋白包括聚精氨酸標(biāo)簽 (Arg-標(biāo)簽)、FLAG-標(biāo)簽、Strep-標(biāo)簽、c-myc-標(biāo)簽、S-標(biāo)簽、鈣調(diào)蛋白結(jié)合肽、纖維素結(jié) 合結(jié)構(gòu)域、SBP-標(biāo)簽,、殼多糖結(jié)合結(jié)構(gòu)域、谷胱甘肽S-轉(zhuǎn)移酶-標(biāo)簽(GST)、麥芽糖結(jié)合 蛋白、轉(zhuǎn)錄終止抗-終止因子(NusA)、大腸桿菌硫氧還蛋白(TrxA)和蛋白質(zhì)二硫鍵異構(gòu)酶 I(DsbA)。優(yōu)選的標(biāo)簽蛋白包括GST。關(guān)于標(biāo)簽蛋白的應(yīng)用的全面討論可參見(jiàn)Terpe等, 標(biāo)簽蛋白融合的綜述從分子和生化基本原理到商業(yè)系統(tǒng)(“Overview of tag protein fusions :frommolecular and biochemical fundamentals to commercial systems)”, Appl. Microbiol. Biotechnol. (2003)60 :523_533。純化后,可任選地從表達(dá)的融合蛋白上去除標(biāo)簽蛋白,即通過(guò)本領(lǐng)域已知的特別 定制的酶法處理。常用的蛋白酶包括腸激酶、煙草蝕紋病毒(TEV)、凝血酶和凝血因子X(jué)a。免疫原性組合物和藥物本文所述組合物優(yōu)選是免疫原性組合物,更優(yōu)選是疫苗組合物。在一些實(shí)施方式 中,組合物的PH為6-8,優(yōu)選約為7??墒褂镁彌_液來(lái)維持pH。該組合物可以是無(wú)菌和/或 無(wú)熱原的。組合物與人體等張。本發(fā)明疫苗可以是預(yù)防性(即預(yù)防感染)或治療性(即治療感染)疫苗,但一般是 預(yù)防性疫苗。因此,提供了在易受肺炎鏈球菌感染的動(dòng)物中治療性或預(yù)防性治療肺炎鏈球 菌感染的方法,該方法包括給予所述動(dòng)物治療或預(yù)防量的本文所述免疫原性組合物。例如, 提供了在易受鏈球菌感染的動(dòng)物中治療性或預(yù)防性治療肺炎鏈球菌感染的方法,該方法包 括給予所述動(dòng)物治療或預(yù)防量的本文所述免疫原性組合物。本文所述組合物也可用作藥物。在一些實(shí)施方式中,藥物優(yōu)選能夠引起哺乳動(dòng)物 的免疫應(yīng)答(即它是一種免疫原性組合物),并且在一些實(shí)施方式中,它是疫苗。本文所述 組合物也可以用于引起哺乳動(dòng)物免疫應(yīng)答的藥物的制備過(guò)程中。在一些實(shí)施方式中,所述 藥物是疫苗。本文所述組合物也可以在含有一個(gè)或多個(gè)組合物容器的試劑盒中使用。這些組合 物可以是液體形式或是凍干形式,各個(gè)抗原也是這樣。組合物合適的容器包括例如瓶、小 瓶、注射器和試管。容器可由多種材料,包括玻璃和塑料制成。容器可具有無(wú)菌進(jìn)入口(例 如,容器可以是靜脈內(nèi)輸液袋或者具有皮下注射針可刺穿塞子的小瓶)。這些組合物可包含 含有一種或多種肺炎鏈球菌菌毛多肽的第一組分。優(yōu)選地,肺炎鏈球菌菌毛多肽是寡聚或 高寡聚形式。試劑盒還可包括含有藥學(xué)上可接受的緩沖劑,例如磷酸鹽緩沖鹽水、林格溶液或 右旋糖溶液的第二容器。試劑盒也可包括適用于最終使用者的其他材料,包括其他緩沖劑、 稀釋劑、填充劑、針和注射器。試劑盒也可包括另一活性劑(例如抗生素)的第二或第三容器。
試劑盒也可包括包裝說(shuō)明書(shū),說(shuō)明書(shū)上寫(xiě)明誘導(dǎo)針對(duì)肺炎鏈球菌的免疫或者用于 治療肺炎鏈球菌感染的方法的指導(dǎo)說(shuō)明。包裝說(shuō)明書(shū)可以是未經(jīng)批準(zhǔn)的說(shuō)明書(shū)草圖,或者 可以是經(jīng)食品藥品管理局(FDA)或其他管理機(jī)構(gòu)批準(zhǔn)的包裝說(shuō)明書(shū)。也可使用預(yù)先填充有本文所述免疫原性組合物的遞送裝置。誘導(dǎo)哺乳動(dòng)物免疫應(yīng)答的方法包括給予有效量的本文所述組合物的步驟。在一些 實(shí)施方式中,免疫應(yīng)答是保護(hù)性的,優(yōu)選涉及抗體和/或細(xì)胞介導(dǎo)的免疫。在一些實(shí)施方式 中,免疫應(yīng)答將誘導(dǎo)長(zhǎng)效(例如中和)抗體以及接觸一種或多種肺炎鏈球菌抗原后快速應(yīng) 答的細(xì)胞介導(dǎo)的免疫。在一些實(shí)施方式中,該方法引起加強(qiáng)的應(yīng)答。哺乳動(dòng)物中中和肺炎鏈球菌感染的方法可包括給予哺乳動(dòng)物有效量的本文所述 的免疫原性組合物,本文所述的疫苗,或者識(shí)別本文所述免疫原性組合物的抗體。在一些實(shí)施方式中,所述哺乳動(dòng)物是人。如果疫苗用作預(yù)防用途,人可以是男性或 女性(不論是生育期或者青春期)。或者,所述人可以是老人(例如,超過(guò)50、55、60、65、70、 75、80或85歲),可能患有潛在的疾病如糖尿病或癌癥。在一些實(shí)施方式中,如果疫苗用作 治療用途,所述人可以是孕婦或老人。在一些實(shí)施方式中,本文所述的用途和方法是用于防止和/或治療肺炎鏈球菌導(dǎo) 致的疾病。該組合物也可有效對(duì)抗其他鏈球菌。該組合物也可有效對(duì)抗其他革蘭氏陽(yáng)性菌。檢測(cè)治療性治療的功效的一些方法涉及在給予本發(fā)明組合物后監(jiān)測(cè)肺炎鏈球菌 感染。檢測(cè)預(yù)防性治療的功效的一種非限制性方式涉及在給予組合物之后監(jiān)測(cè)針對(duì)本文所 述組合物中肺炎鏈球菌抗原的免疫應(yīng)答。評(píng)價(jià)本文所述免疫原性組合物的組分蛋白的免疫原性的非限制性方式是重組表 達(dá)該蛋白并通過(guò)免疫印跡方法篩選患者血清或粘膜分泌物。蛋白質(zhì)和患者血清之間的陽(yáng)性 反應(yīng)表明該患者已對(duì)所研究蛋白質(zhì)產(chǎn)生免疫應(yīng)答,即該蛋白是免疫原。也可利用該方法鑒 定優(yōu)勢(shì)免疫蛋白和/或表位。檢測(cè)治療性治療的功效的另一種方式涉及在給予本發(fā)明組合物后監(jiān)測(cè)肺炎鏈球 菌感染。檢測(cè)預(yù)防性治療的功效的一種方式涉及在給予組合物后監(jiān)測(cè)針對(duì)本文所述組合物 中肺炎鏈球菌抗原的全身免疫應(yīng)答(例如監(jiān)測(cè)IgGl和IgG2a產(chǎn)生水平)和粘膜免疫應(yīng)答 (例如監(jiān)測(cè)IgA產(chǎn)生水平)。通常,肺炎鏈球菌血清特異性抗體應(yīng)答在免疫后、刺激前進(jìn)行 測(cè)定,而粘膜肺炎鏈球菌特異性抗體應(yīng)答在免疫后、刺激后測(cè)定。在一些實(shí)施方式中,本文所述疫苗組合物給予宿主(例如人)之前可以在體外和 體內(nèi)動(dòng)物模型中進(jìn)行評(píng)價(jià)。本文所述免疫原性組合物的功效也可以通過(guò)用免疫原性組合物刺激肺炎鏈球菌 感染的動(dòng)物模型(例如豚鼠或小鼠)進(jìn)行體內(nèi)測(cè)定。免疫原性組合物可源自與刺激血清型 相同或不同的血清型。在一些實(shí)施方式中,免疫原性組合物可源自與刺激血清型相同的血 清型。在一些實(shí)施方式中,免疫原性組合物和/或刺激血清型可源自肺炎鏈球菌的血清型。體內(nèi)功效模型包括但不限于(i)使用人肺炎鏈球菌血清型的鼠感染模型;(ii) 鼠疾病模型,這是一種采用鼠適應(yīng)性肺炎鏈球菌菌株,例如在小鼠中特別有毒力的菌株的 鼠模型;和(iii)使用人肺炎鏈球菌分離物的靈長(zhǎng)類(lèi)模型。免疫應(yīng)答可以是TH1免疫應(yīng)答和TH2免疫應(yīng)答之一或兩者。免疫應(yīng)答可以是改善 的、或提高的、或改變的免疫應(yīng)答。免疫應(yīng)答可以是全身免疫應(yīng)答和粘膜免疫應(yīng)答之一或兩者。在一些實(shí)施方式中,免疫應(yīng)答是提高的全身應(yīng)答和/或粘膜應(yīng)答。提高的全身免疫和/ 或粘膜免疫表現(xiàn)為提高的TH1和/或TH2免疫應(yīng)答。在一些實(shí)施方式中,提高的免疫應(yīng)答 包括IgGl和/或IgG2a和/或IgA產(chǎn)生增加。在一些實(shí)施方式中,粘膜免疫應(yīng)答是TH2免 疫應(yīng)答。在一些實(shí)施方式中,粘膜免疫應(yīng)答包括IgA產(chǎn)生增加?;罨腡H2細(xì)胞提高抗體產(chǎn)生,因而在應(yīng)對(duì)胞外感染中有價(jià)值?;罨腡H2細(xì)胞 可分泌IL-4、IL-5、IL-6和IL-10中的一種或多種。TH2免疫應(yīng)答可導(dǎo)致產(chǎn)生IgGl、IgE、 IgA和記憶B細(xì)胞,用于將來(lái)的保護(hù)作用。TH2免疫應(yīng)答可包括一種或多種與TH2免疫應(yīng)答相關(guān)的細(xì)胞因子(例如IL_4、 IL-5、IL-6和IL-10)中的一種或多種增加,或者IgGl、IgE、IgA和記憶B細(xì)胞產(chǎn)生增加。 在一些實(shí)施方式中,提高的TH2免疫應(yīng)答將包括IgGl產(chǎn)生的增加。TH1免疫應(yīng)答可包括CTL中的一種或多種增加,與TH1免疫應(yīng)答相關(guān)的細(xì)胞因子 (例如IL-2、IFNy和TNF3 )中的一種或多種增加,活化的巨噬細(xì)胞增加,NK活性增加,或 者IgG2a產(chǎn)生增加。在一些實(shí)施方式中,提高的TH1免疫應(yīng)答將包括IgG2a產(chǎn)生的增加。本文所述免疫原性組合物,特別是包含一種或多種肺炎鏈球菌多肽抗原的免疫原 性組合物,可單獨(dú)使用或與其他抗原以及任選地與能夠引發(fā)Thl和/或Th2應(yīng)答的免疫調(diào) 節(jié)劑聯(lián)用。本文所述組合物通常直接給予患者。在一些實(shí)施方式中,對(duì)于某些組合物宜采用 某些途徑,以便產(chǎn)生更有效的免疫應(yīng)答,CMI應(yīng)答,或引起副作用可能性較低,或者更容易給 予。可通過(guò)胃腸道外注射(如皮下、腹膜內(nèi)、皮內(nèi)、靜脈內(nèi)、肌內(nèi)或給予組織間隙),或通過(guò)直 腸、口服(例如片劑、噴霧劑)、陰道、局部、透皮(例如參見(jiàn)W0 99/27961)或經(jīng)皮(例如參 見(jiàn)TO 02/074244和W0 02/064162)、鼻內(nèi)(例如參見(jiàn)W003/028760)、眼部、耳內(nèi)、經(jīng)肺或其 它粘膜給藥途徑進(jìn)行直接遞送。可采用本文所述組合物引發(fā)全身和/或粘膜免疫。在一些實(shí)施方式中,免疫原性組合物包含一種或多種可引發(fā)中和性抗體應(yīng)答的肺 炎鏈球菌多肽抗原以及一種或多種可引發(fā)細(xì)胞介導(dǎo)免疫應(yīng)答的肺炎鏈球菌多肽抗原。這 樣,中和性抗體應(yīng)答可防止或抑制初始肺炎鏈球菌感染,而能夠引發(fā)提高的Thl細(xì)胞應(yīng)答 的細(xì)胞介導(dǎo)免疫應(yīng)答可進(jìn)一步防止肺炎鏈球菌廣泛的擴(kuò)散。免疫原性組合物可包含一種或 多種肺炎鏈球菌多肽抗原;一種或多種肺炎鏈球菌菌毛或其他肺炎鏈球菌抗原;以及一種 或多種非菌毛肺炎鏈球菌抗原,例如胞質(zhì)抗原。在一些實(shí)施方式中,免疫原性組合物包含一 種或多種肺炎鏈球菌表面抗原等以及一種或多種其他抗原,例如能夠引發(fā)Thl細(xì)胞應(yīng)答的 胞質(zhì)抗原??梢酝ㄟ^(guò)單劑量方案或多劑量方案進(jìn)行劑量治療。多劑量可用于初免方案和/或 加強(qiáng)免疫方案。在多劑量方案中,可通過(guò)相同或不同途徑給予各種劑量,例如初免采用胃腸 道外途徑而加強(qiáng)免疫采用粘膜途徑,或者初免采用粘膜途徑而加強(qiáng)免疫采用胃腸道外途徑寸。本文所述組合物可以制備成多種形式。例如,可將該組合物制備成液體溶液或懸 浮液形式的注射劑。也可制備適合在注射前溶解或懸浮于液體運(yùn)載體的固體形式(如凍干 組合物)。該組合物可制備成局部制劑,如油膏劑、乳膏劑或粉末劑。該組合物可制備成口 服給藥制劑,如片劑或膠囊,噴霧劑,或糖漿劑(任選調(diào)味)。該組合物可制備成使用細(xì)粉或噴霧的肺部給藥制劑,如吸入劑。該組合物可制備成栓劑或子宮托。該組合物可制成鼻內(nèi)、 耳內(nèi)或眼內(nèi)給藥,例如滴劑。該組合物可以是藥盒形式,設(shè)計(jì)成臨給予患者之前重建合并的 組合物。這種藥盒可包含一種或多種液體形式的抗原以及一種或多種凍干抗原。用作疫苗的免疫原性組合物包含免疫有效量的抗原,以及需要的任何其它組分, 例如抗生素?!懊庖哂行Я俊敝敢砸淮蝿┝炕蛞幌盗袆┝康囊徊糠郑瑢⒛硠┝拷o予個(gè)體能有 效治療或預(yù)防,或者提高可恒量的免疫應(yīng)答,或者防止或減輕臨床癥狀。此量取決于所治療 個(gè)體的健康和身體狀況、年齡、所治療個(gè)體的分類(lèi)地位(如非人靈長(zhǎng)動(dòng)物、靈長(zhǎng)動(dòng)物等)、個(gè) 體的免疫系統(tǒng)合成抗體的能力、所需的保護(hù)程度、疫苗配方、治療醫(yī)生對(duì)醫(yī)學(xué)情況的評(píng)估和 其它相關(guān)因素。預(yù)計(jì)該量將落入可通過(guò)常規(guī)試驗(yàn)測(cè)定的相對(duì)較寬的范圍內(nèi)。組合物的其他組分除上述組分外,本文所述組合物還可包含一種或多種“藥學(xué)上可接受的載體”,其 包括本身不誘導(dǎo)產(chǎn)生對(duì)接受該組合物的個(gè)體有害的抗體的任何載體。合適的載體一般是代 謝慢的大分子,如蛋白質(zhì)、多糖、聚乳酸、聚乙醇酸、聚氨基酸、氨基酸共聚物和脂質(zhì)聚集體 (如油滴或脂質(zhì)體)。本領(lǐng)域技術(shù)人員熟知這類(lèi)載體。疫苗也可含有稀釋劑,如水、鹽水、甘 油等。此外,也可存在輔助劑,如濕潤(rùn)劑或乳化劑、PH緩沖劑等。藥學(xué)上可接受的賦形劑的 充分討論參見(jiàn)Gennaro (2000)《雷明登藥物科學(xué)與實(shí)踐》(Remington :The Science and Practice ofPharmacy),第 20 版,ISBN 0683306472.。佐齊[J本文所述疫苗可與其他免疫調(diào)節(jié)劑聯(lián)合給予。在一些實(shí)施方式中,組合物還包含 一種或多種佐劑。用于本文所述疫苗的佐劑包括但不限于以下所述一種或多種含礦物質(zhì)的組合物本發(fā)明中適合用作佐劑的含有礦物質(zhì)的組合物包括礦物鹽,例如鋁鹽和鈣鹽。本 發(fā)明包括礦物鹽,例如氫氧化物(如羥基氧化物)、磷酸鹽(如羥基磷酸鹽、正磷酸鹽)、 硫酸鹽等(例如參見(jiàn)《疫苗設(shè)計(jì)》(Vaccine Design) (1995),Powell和Newman編,ISBN 030644867X. Plenum的第8和9章),或不同礦物質(zhì)化合物的混合物(例如,磷酸鹽和氫氧化 物佐劑的混合物,任選地磷酸鹽過(guò)量),這些化合物可采取任何合適的形式(如凝膠、晶體、 無(wú)定形等),優(yōu)選吸附于鹽。含有礦物質(zhì)的組合物也可配制為金屬鹽顆粒(W0 00/23105)。本文所述疫苗中可包含鋁鹽,使Al3+劑量在每劑0. 2到1. 0毫克之間。油乳劑適合用作本發(fā)明佐劑的油乳劑組合物包括角鯊烯_水乳劑,例如MF59 (利用微流 化床配制成亞微米顆粒的5%角鯊烯、0. 5%吐溫80和0. 5%司盤(pán)85)。參見(jiàn)W090/14837。也 可參見(jiàn)Podda,含新型佐劑的含佐劑流感疫苗含MF-59佐劑疫苗的經(jīng)歷(“The adjuvanted influenza vaccines with novel adjuvants :experiencewith the MF59_adjuvanted vaccine”),Vaccine (2001) 19 =2673-2680 ;Frey 等,在除老人以外的成人對(duì)象中含 MF-59 佐 劑的流感疫苗與不含佐劑的流感疫苗的安全性、耐受性和免疫原性的比較(“Comparison of the safety, tolerability andimmunogenicity of a MF59-adjuvanted influenza vaccine and a non-adjuvantedinfluenza vaccine in non-elderly adults"), Vaccine (2003) 21 :4234-4237。MF59用作FLUAD 流感病毒三價(jià)亞基疫苗的佐劑。在一些實(shí)施方式中,用于該組合物中的佐劑為亞微米水包油乳劑。本發(fā)明采用的亞微米水包油乳劑優(yōu)選為鯊烯/水乳劑,任選地包含不同量的MTP-PE,如含有4-5% (重量 /體積)鯊烯、0.25-1.0% (重量/體積)吐溫80 (聚氧乙烯脫水山梨糖醇單油酸酯)、和 /或0. 25-1. 0%的司盤(pán)85 (脫水山梨糖醇三油酸酯)以及任選的N-乙酰胞壁?;?L-丙 氨?;?D-異谷氨酰氨酰基-L-丙氨酸-2- (1’ -2 ’ - 二棕櫚?;?sn-甘油_3_羥基磷酰氧 基)-乙胺(MTP-PE)的亞微米水包油乳劑,例如,稱(chēng)為“MF59”的亞微乳水包油乳劑(國(guó)際 公開(kāi)WO 90/14837 ;美國(guó)專(zhuān)利6,299,884和6,451,325,其內(nèi)容被納入本文作為參考;和Ott 等,MF-59 人用疫苗佐劑的設(shè)計(jì)與安全性和效力的評(píng)價(jià)(“MF59—Design and Evaluation of a Safe and Potent Adjuvant forHuman Vaccines,,,《疫苗設(shè)計(jì)亞基與佐劑方法》 (Vaccine Design :The Subunitand Adjuvant Approach) (Powell,M. F.禾口Newman,M. J.編) Plenum Press,紐約,1995,第277-296頁(yè))。MF59包含4-5% (重量/體積)鯊烯(例如 4. 3% ),0. 25-0. 5% (重量/體積)吐溫80 和0. 5% (重量/體積)司盤(pán)85 ,以及任選 地含有各種含量的MTP-PE,利用微流化床如110Y型微流化床(馬薩諸塞州牛頓市的微流化 床公司(Microfluidics,Newton,MA)配制成亞微米水包油乳劑。 例如,MTP-PE的用量約為 0-500微克/劑量,更優(yōu)選0-250微克/劑量,最優(yōu)選0-100微克/劑量。如本文所用,術(shù)語(yǔ) “MF59-0”表示不含MTP-PE的上述亞微米水包油乳劑,而術(shù)語(yǔ)MF59-MTP表示含MTP-PE的制 齊U。例如,“MF59-100”包含100微克MTP-PE/劑量,等等。本文所用的另一種亞微米水包油 乳劑MF69包含4. 3 % (重量/體積)鯊烯、0. 25 % (重量/體積)吐溫80 和0. 75 % (重 量/體積)司盤(pán)85 以及任選的MTP-PE。另一種亞微米水包油乳劑是MF75,也稱(chēng)為SAF, 包含10%鯊烯,0. 4%吐溫80 ,5%普流羅尼-嵌段聚合物L(fēng)121和thr_MDP,也可微流化形 成亞微米乳劑。MF75-MTP表示包含MTP的MF75,例如每劑量包含100-400微克MTP-PE。國(guó)際公開(kāi)WO 90/14837和美國(guó)專(zhuān)利6,299,884和6,451,325 (納入本文作為參考) 中詳細(xì)描述了用于組合物的亞微米水包油乳劑、其制備方法和免疫刺激劑如胞壁酰肽。還可將完全弗氏佐劑(CFA)和不完全弗氏佐劑(IFA)用作本發(fā)明組合物的佐劑。皂苷制劑皂苷制劑也可用作本文所述組合物的佐劑。皂苷是在許多種類(lèi)植物的樹(shù)皮、葉、莖 干、根甚至花中發(fā)現(xiàn)的留醇糖苷和三萜糖苷的異質(zhì)群體。已廣泛研究了作為佐劑的來(lái)自皂 樹(shù)(Quillaia saponaria)Molina樹(shù)皮的皂苷。皂苷也可獲自麗花菝葜(Smilax ornata) (墨西哥菝葜)、滿天星(Gypsophilla paniculata)(婚紗花)和肥皂草(Saponaria officianalis)(皂根)。皂苷佐劑制劑包括純化制劑如QS21以及脂質(zhì)制劑如ISC0M。已采用高效薄層色譜(HP-TLC)和反相高效液相色譜(RP-HPLC)對(duì)皂苷組合物進(jìn) 行純化。已鑒定了用這些技術(shù)純化的特定組分,包括QS7、QS17、QS18、QS21、QH-A, QH-B和 QH-C0制備QS21的方法參見(jiàn)美國(guó)專(zhuān)利5,057,540。皂苷制劑也可包含留醇,如膽固醇(參 見(jiàn) W096/33739)。皂苷和膽固醇的組合可用于形成稱(chēng)為免疫刺激復(fù)合物(ISCOM)的獨(dú)特顆粒。 ISCOM通常也含有磷脂如磷脂酰乙醇胺或磷脂酰膽堿。ISCOM中可采用任何已知的皂苷。 ISCOM優(yōu)選包含QuilA、QHA和QHC中的一種或多種。ISCOM可進(jìn)一步參見(jiàn)EP0109942、WO 96/11711和WO 96/33739。任選地,ISCOM可不含其它去污劑。參見(jiàn)WO 00/07621。開(kāi)發(fā)基于皂苷的佐劑的綜述可參見(jiàn)Barr等,ISCOM和其他基于皂苷的佐 齊[J ( "ISCOMs and other saponin based adjuvants") , Advanced Drug DeliveryReviews (1998) 32 :247_271。也可參見(jiàn)Sjolander等,口服遞送的皂苷和ISCOM疫苗的攝 Φ·禾口舌 生("Uptake and adjuvant activity of orally delivered saponin and ISCOMvaccines”),Advanced Drug Delivery Reviews (1998) 32 :321_338。病毒體和病毒樣顆粒(VLP)病毒體和病毒樣顆粒(VLP)也可用作本發(fā)明組合物的佐劑。這些結(jié)構(gòu)通常包 含一種或多種任選地與磷脂組合或一起配制的病毒蛋白。它們通常無(wú)病原性、不能復(fù) 制,通常不含任何天然病毒基因組。可用重組方法產(chǎn)生或從全病毒分離得到這種病毒 蛋白。這些適用于病毒體或VLP中的病毒蛋白包括來(lái)源于流感病毒(例如HA或NA)、 乙肝病毒(例如核心蛋白或包膜蛋白)、戊肝病毒、麻疹病毒、辛德比斯病毒、輪狀病 毒、口蹄疫病毒、逆轉(zhuǎn)錄病毒、諾瓦克病毒、人乳頭狀瘤病毒、HIV, RNA-噬菌體、Qi3-噬 菌體(例如外殼蛋白)、GA-噬菌體、fr-噬菌體、AP205噬菌體和Ty (例如反轉(zhuǎn)錄轉(zhuǎn)座 子 Ty 蛋白 pi)的蛋白。VLP 在 WO 03/024480、WO 03/024481 和 Niikura 等,“嵌合重 組戊型肝炎病毒樣顆粒作為呈遞外來(lái)表位的口服疫苗載體”(“Chimeric Recombinant Hepatitis E Virus-Like Particles as anOral Vaccine Vehicle Presenting Foreign Epitopes”),Virology (2002) 293 273-280 ;Lenz 等,“乳頭狀瘤病毒樣顆粒誘導(dǎo)樹(shù)突 ^iffllfi WiliiiS^" ( "Papillomarivurs-Like Particles Induce Acute Activation of Dendritic Cells”),Journalof Immunology (2001) 5246-5355 ;Pinto 等,“用重 組HPV-16L1病毒樣顆粒免疫的健康志愿者對(duì)乳頭狀瘤病毒(HPV)-16L1的細(xì)胞免疫應(yīng) 答”("Cellular ImmuneResponses to Human Papillomavirus (HPV) -16L IHealthy Volunteers Immunizedwith Recombinant HPV-16L IVirus-Like Particles,,), Journal of Infectious Diseases (2003) 188 :327_338 ;和 Gerber 等,“與大腸桿菌熱不穩(wěn)定腸 毒素突變體R192G或CpG共同給予時(shí)人乳頭狀瘤病毒病毒樣顆粒是有效的口服免疫 原” ("HumanPapillomavirus Virus-Like Particles Are Efficient Oral Immunogens whenCoadministered with Escherichia coli Heat-Labile Enterotoxin Mutant R192G orCpG”),Journal of Virology (2001) 75 (10) :4752_4760 中進(jìn)一步討論。病毒體在例如 Gluck等,“未來(lái)疫苗開(kāi)發(fā)的新技術(shù)平臺(tái)”(“New Technology Platforms in theDevelopment of Vaccines for the Future,,),Vaccine (2002) 20 :B10_B16 中進(jìn)一步討論。免疫增強(qiáng)的 重建流感病毒體(IRIV)可用作鼻內(nèi)三價(jià)INFLEXAL 產(chǎn)品{Mischler和Metcalfe (2002) Vaccine 20增補(bǔ)5 :B17_23}和INFLUVAC PLUS 產(chǎn)品的亞單位抗原遞送系統(tǒng)。細(xì)菌或微生物衍生物適用于本發(fā)明組合物的佐劑包括細(xì)菌或微生物衍生物,例如(a)腸細(xì)菌脂多糖(LPS)的無(wú)毒性衍生物這些衍生物包括單磷酰脂質(zhì)A (MPL)和3_0_脫酰基MPL (3dMPL)。3dMPL是具有4、 5或6?;湹?脫-0-?;鶈瘟柞V|(zhì)A的混合物。3脫-0-酰基單磷酰脂質(zhì)A的優(yōu)選 “小顆?!毙问揭?jiàn)EP O 689 454中所述。3dMPL的這種“小顆?!毙〉阶阋栽谶^(guò)濾除菌時(shí)通 過(guò)0.22 μ m膜(參見(jiàn)EP 0689454)。其它無(wú)毒LPS衍生物包括單磷酰脂質(zhì)A模擬物,例如 氨基烷基氨基葡萄糖苷磷酸鹽衍生物如RC-529。參見(jiàn)Johnson等(1999)Bi00rg Med Chem Lett 9 :2273-2278。(b)脂質(zhì)A衍生物
脂質(zhì)A衍生物包括大腸桿菌(Escherichia coli)的脂質(zhì)A衍生物,如0M-174。 0M-174參見(jiàn)例如Meraldi等,“0M-174,一種具有人用價(jià)值的新型佐劑,與由柏格鼠瘧原蟲(chóng) 的環(huán)孢子蛋白合成的C-末端片段一起給予可誘導(dǎo)保護(hù)性應(yīng)答”(“0M_174,a New Adjuvant with a Potential for Human Use, Induces a ProtectiveResponse with Administered with the Synthetic C-Terminal Fragment 242—310 fromthe circumsporozoite protein of Plasmodium berghei ”),Vaccine (2003) 21 :2485_2491 ;和 Pajak 等,“佐劑 0M-174 可誘 導(dǎo)體內(nèi)鼠樹(shù)突狀細(xì)胞的遷移和成熟”(“TheAdiuvant OM-174 induces both the migration and maturation of murine dendritic cellsin vivo,,),Vaccine(2003) 21 :836_842。(c)免疫刺激性寡核苷酸適合用作本發(fā)明組合物的佐劑的免疫刺激性寡核苷酸包括含CpG基序的核苷酸序列(含有通過(guò)磷酸酯鍵連接的非甲基化胞嘧啶和鳥(niǎo)嘌呤核苷的序列)。含有回文或聚 (dG)序列的細(xì)菌雙鏈RNA或寡核苷酸也顯示出免疫刺激性。CpG可包含核苷酸修飾/類(lèi)似物,如硫代磷酸酯修飾,可以是雙鏈或單鏈。任 選地,鳥(niǎo)苷可被類(lèi)似物如2’ -脫氧-7-脫氮鳥(niǎo)苷取代??赡艿念?lèi)似替代物的例子參 見(jiàn)Kandimalla等,“各種合成的核苷酸基序識(shí)別模式具有獨(dú)特細(xì)胞因子誘導(dǎo)特性的強(qiáng) 效免疫調(diào)節(jié)性寡脫氧核苷酸試劑的設(shè)計(jì)與開(kāi)發(fā)”(“Divergent syntheticnucleotide motif recognition pattern :design and development of potentimmunomodulatory oligodeoxyribonucleotide agents with distinct cytokine inductionprofi1es,,), Nucleic Acids Research(2003)31(9) 2393-2400 ;W002/26757 和 W099/62923。Krieg, "CpG 基序細(xì)菌提取物中的活性成分?”( “CpG motifs :theactive ingredient in bacterial extracts ?”),Nature Medicine (2003) 9 (7) :831_835 ;McCluskie 等,“小鼠 中用乙肝表面抗原和CpG DNA的胃腸外和粘膜初免-加強(qiáng)免疫方案”(“Parenteral and mucosal prime-boost immunization strategies in mice withhepatitis B surface antigen and CpG DNA"),FEMS Immunology and MedicalMicrobiology(2002)32 179-185 ; W098/40100 ;美國(guó)專(zhuān)利6,207,646 ;美國(guó)專(zhuān)利6,239,116和美國(guó)專(zhuān)利6,429,199.中進(jìn)一步 討論了 CpG寡核苷酸的佐劑作用。CpG 序列可能導(dǎo)向 TLR9,例如基序 GTCGTT (SEQ ID NO 22)或 TTCGTT (SEQ ID N0:23)。參見(jiàn)Kandimalla等,“Toll樣受體9 新型合成CpG DNA調(diào)節(jié)識(shí)別和細(xì)胞因子 誘導(dǎo),,("Toll-like receptor 9 !modulation of recognition and cytokine induct ion by novel synthetic CpG DNAs,,),Biochemical Society Transactions(2003)31 (第 3部分)654-658。CpG序列可特異性誘導(dǎo)Thl免疫應(yīng)答,例如CpG-A 0DN,或更特異地 誘導(dǎo) B 細(xì)胞應(yīng)答,例如 CpG-B ODN。CpG-A 禾Π CpG-B ODN 在 Blackwell 等,“ CpG-A-誘 導(dǎo)的單核細(xì)胞IFN-Y-可誘導(dǎo)的蛋白-10產(chǎn)生受類(lèi)漿細(xì)胞樹(shù)突狀細(xì)胞衍生的IFN-a 的 調(diào) 控,,(“CpG-A-Induced MonocyteIFN-gamma-InducibIe Protein-IOProduction is Regulated by Plasmacytoid DendriticCell Derived IFN-alpha,,),J.Immunol. (2003) 170(8) 4061-4068 ;Krieg,‘‘CpG 的 A 至Ij Z” ( "From A to Z on CpG”),TRENDS in Immunology (2002) 23 (2) :64_65 和 W001/95935 中討論。CpG 優(yōu)選是 CpG-A 0DN。在一些實(shí)施方式中,構(gòu)建CpG寡核苷酸時(shí)使其5’端可為受體所識(shí)別。任選將兩 個(gè)CpG寡核苷酸序列的3’端相連接形成“免疫聚體”。例如參見(jiàn)Kandimalla等,“CpG寡核苷酸的二級(jí)結(jié)構(gòu)影響免疫剌激活性”(“Secondary structures in CpGoligonucleotides affect immunostimulatory activity,,),BBRC (2003) 306 :948-953 ;Kandimalla 等,“Toll-樣受體9 新型合成的GpG DNA調(diào)節(jié)識(shí)別和細(xì)胞因子誘導(dǎo)”(“Toll-like receptor 9 -modulation of recognition and cytokine induction by novelsynthetic GpG DNAs"), Biochemical Society Transactions(2003)31 (第 3 部分)664_658 ; Bhagat等,“ CpG五-和六脫氧核糖核苷酸作為強(qiáng)效免疫調(diào)節(jié)劑”(“ CpG penta-and hexadeoxyribonucIeotides as potent immunomodulatory agents,,)BBRC(2003)300 : 853-861和 WO 03/035836。(d)ADP-核糖基化毒素及其脫毒的衍生物細(xì)菌ADP-核糖基化毒素及其脫毒衍生物可用作本發(fā)明組合物的佐劑。在一些 實(shí)施方式中,該蛋白獲自大腸桿菌(大腸桿菌不耐熱腸毒素“LT”)、霍亂(“CT”)菌或 百日咳(“PT”)菌。W095/17211中描述了將脫毒的ADP-核糖基化毒素用作粘膜佐劑, W098/42375中描述了將其用作胃腸道外佐劑。在一些實(shí)施方式中,佐劑是脫毒的LT突 變體如LT-K63、LT-R72和LT-192G。以下參考文獻(xiàn)中描述了將ADP-核糖基化毒素及其 脫毒衍生物,尤其是LT-K63和LT-R72用作佐劑,這些文獻(xiàn)各自的內(nèi)容被具體納入本文作 為參考=Beignon等,“大腸桿菌不耐熱腸毒素的LTR72突變體增強(qiáng)肽抗原引發(fā)CD4+T細(xì) 胞和在輔助施加到裸露皮膚上之后分泌Y-干擾素的能力”(“The LTR72 Mutant of Heat-Labile Enterotoxin ofEscherichia coli Enhances the Ability of Peptide Antigens to Elicit CD4+T Cells andSecrete Gamma Interferon after Coapplication onto Bare Skin”),Infection andlmmunity (2002) 70 (6) :3012_3019 ;Pizza 等,“粘膜疫 苗LT 和 CT 的無(wú)毒衍生物作為粘膜佐劑” ("Mucosal vaccines :non toxic derivatives of LT and CT as mucosaladjuvants) Vaccine (2001) 19 2534-2541 ;Pizza ^,"LTK63 和 LTR72,兩種適合臨床試驗(yàn)的粘膜佐劑”(‘‘LTK63 and LTR72, two mucosal adjuvants ready forclinical trials") , Int.J. Med. Microbiol(2000) 290 (4-5) 455-461 ; Scharton-Kersten等,“用細(xì)菌ADP-核糖基化外毒素、亞單位和無(wú)關(guān)佐劑進(jìn)行經(jīng)皮免 疫,,(“Transcutaneous Immunization with Bacterial ADP-Ribosylating Exotoxins, Subunitsand Unrelated Adjuvants"),Infection and Immunity(2000)68(9) :5306_5313 ; Ryan等,“大腸桿菌不耐熱腸毒素的突變體有效用作鼻腔遞送無(wú)細(xì)胞百日咳疫苗的粘膜佐 劑無(wú)毒AB復(fù)合物和酶活性對(duì)Thl和Th2細(xì)胞的差別作用” ("Mutants ofEscherichia coli Heat-Labile Toxin Act as Effective Mucosal Adjuvants for NasalDelivery of an Acellular Pertussis Vaccine -Differential Effects of the Nontoxic ABComplex and Enzyme Activity on Th 1 and Th2Cells”),Infection and Immunity (1999)67(12) 6270-6280 ;Partidos等,“大腸桿菌的不耐熱腸毒素及其位點(diǎn)導(dǎo)向突變體LTK63提高對(duì) 鼻內(nèi)共同免疫合成肽的增殖性和細(xì)胞毒性T細(xì)胞應(yīng)答”(“Heat-labileenterotoxin of Escherichia coli and its site-directed mutant LTK63enhance theproliferative and cytotoxic T-cell responses to intranasally co-immunized syntheticpeptides,,), Immunol. Lett. (1999)67(3) :209_216 ;Peppoloni等,“大腸桿菌不耐熱腸毒素的突變體 用作鼻內(nèi)遞送疫苗的安全強(qiáng)效佐劑”(“Mutents of the Escherichiacoli heat-labile enterotoxin as safe and strong adjuvants for intranasal delivery ofvaccines"),Vaccines (2003) 2 (2) :285_293 ;和Pine等,(2002) “用流感疫苗和大腸桿菌不耐熱腸毒素的脫毒突變體進(jìn)行鼻內(nèi)免疫,,(“Intranasal immunization withinfluenza vaccine and a detoxified mutant of heat labile enterotoxin from Escherichiacoli (LTK63),,, J. Control Release (2002) 85 (1-3) :263_270。 優(yōu)選根據(jù) Domenighini 等,Mol. Microbiol (1995) 15(6) 1165-1167中提出的ADP-核糖基化毒素的A和B亞單位的排列對(duì) 比對(duì)氨基酸取代基編號(hào),該參考文獻(xiàn)的全部?jī)?nèi)容特別納入本文作為參考。生物粘附劑和粘膜粘附劑生物粘附劑和粘膜粘附劑也可用作本發(fā)明的佐劑。合適的生物粘附劑包括酯化透 明質(zhì)酸微球(Singh等(2001) J. Cont. Rele. 70 :267_276),或粘膜粘附劑如聚(丙烯酸)、聚 乙烯醇、聚乙烯吡咯烷酮、多糖和羧甲基纖維素的交聯(lián)衍生物。殼聚糖及其衍生物也可用作 本發(fā)明的佐劑。例如參見(jiàn)WO 99/27960。微粒微粒也可用作本文所述組合物的佐劑。微粒(即粒徑約lOOnm-150 μ m,更優(yōu)選約 200nm-30 μ m,最優(yōu)選約500nm-10 μ m)由生物可降解的無(wú)毒材料(例如聚(α -羥酸)、聚 羥基丁酸、聚原酸酯、聚酐、聚己內(nèi)酯等),優(yōu)選聚(丙交酯-乙交酯共聚物)形成,并任選 經(jīng)處理而具有帶負(fù)電荷表面(例如用SDS處理)或帶正電荷表面(例如用陽(yáng)離子去污劑如 CTAB處理)。脂質(zhì)體適合用作佐劑的脂質(zhì)體制劑的例子在美國(guó)專(zhuān)利6,090, 406、美國(guó)專(zhuān)利5,916,588 和EP 0 626 169中描述。聚氧乙烯醚和聚氧乙烯酯制劑適合用于本文所述組合物的佐劑包括聚氧乙烯醚和聚氧乙烯酯。參見(jiàn) W099/52549。這種制劑還包括聚氧乙烯去水山梨糖醇酯表面活性劑和辛苯聚醇 (W001/21207)以及聚氧乙烯烷基醚或酯表面活性劑和至少一種其它非離子型表面活性劑 如辛苯聚醇(W0 01/21152)的混合物。在一些實(shí)施方式中,聚氧乙烯醚選自下組聚氧乙烯-9-月桂醚(月桂醇聚醚9)、 聚氧乙烯-9-硬脂?;?steoryl)醚、聚氧乙烯_8_硬脂?;?、聚氧乙烯_4_月桂醚、聚 氧乙烯-35-月桂醚和聚氧乙烯-23-月桂醚。聚磷腈(PCPP)PCPP制劑例如在Andrianov等,“通過(guò)聚磷腈水溶液的凝聚來(lái)制備水 疑 月交 微 球,,("Preparation of hydrogel microspheres by coacervation of aqueouspolyphophazene solutions,,), Biomaterials(1998) 19(1~3) 109-115 禾口 Payne 等,“從聚磷腈基質(zhì)釋放蛋白”(“Protein Release from Polyphosphazene Matrices,,), Adv. Drug. Delivery Review(1998) 31 (3) :185_196 中描述。胞壁酰肽適合用作本發(fā)明佐劑的胞壁酰肽的例子包括N-乙?;鵢胞壁酰-L-蘇氨酰-D-異 谷酰胺(thr-MDP)、N-乙酰基-正胞壁酰-L-丙氨酰-D-異谷酰胺(正-MDP)和N-乙酰胞 壁酰-L-丙氨酰-D-異谷氨酰胺酰-L-丙氨酸-2-(1’ -2’ - 二棕櫚酰-sn-甘油-3-羥基 磷酰氧基)_乙胺MTP-PE)。
咪唑并喹諾酮化合物。適合用作本文所述組合物的佐劑的咪唑并喹諾酮化合物的例子包括咪喹莫特(Imiquamod)及其類(lèi)似物,在Stanley,“咪喹莫特和咪唑并喹諾酮作用機(jī)制與治療效 果,,(“Imiquimod and the imidazoquinolones :mechanism of action andtherapeutic potential”),Clin Exp Dermatol (2002) 27 (7) :571_577 和 Jones, “瑞喹莫德 3M”( “Resiquimod 3M”),Curr Opin Investig Drugs (2003) 4 (2) :214_218 中進(jìn)一步描述。本文所述組合物也可包含上述佐劑的組合。例如,以下佐劑組合物可用于本文所 述的組合物(1)皂苷和水包油乳劑(TO 99/11241);(2)皂苷(例如QS21) +無(wú)毒性LPS衍生物(例如3dMPL)(參見(jiàn)W094/00153);(3)皂苷(例如QS21) +無(wú)毒性LPS衍生物(例如3dMPL) +膽固醇;(4)皂苷(例如 QS21) +3dMPL+IL-12 (任選地 + 甾醇)(W0 98/57659);(5) 3dMPL與例如QS21和/或水包油乳劑的組合(參見(jiàn)歐洲專(zhuān)利申請(qǐng)0835318、 0735898 和 0761231);(6)SAF,含10%角鯊?fù)椤?.4%吐溫80、5%普流羅尼嵌段聚合物L(fēng)121和thr-MDP, 微流化形成亞微米乳劑或渦旋形成較大粒徑的乳劑;(7)Ribi 佐劑體系(RAS) (Ribi Immunochem),含有 2%鯊烯、0. 2%吐溫 80 和一 種或多種細(xì)菌細(xì)胞壁組分,所述組分選自單磷酰脂質(zhì)A(MPL)、海藻糖二霉菌酸酯(TDM)或 細(xì)胞壁骨架(CWS),優(yōu)選 MPL+CWS (Detox );(8) 一種或多種無(wú)機(jī)鹽(例如鋁鹽)+無(wú)毒性LPS衍生物(例如3dMPL)。(9) 一種或多種無(wú)機(jī)鹽(例如鋁鹽)+免疫調(diào)節(jié)性寡核苷酸(例如包含CpG基序的 核苷酸序列)。組合(9)是一種優(yōu)選的佐劑組合。人免疫調(diào)節(jié)劑適合用作本文所述組合物的佐劑的人免疫調(diào)節(jié)劑包括細(xì)胞因子,如白介素(如 IL-I、IL-2、IL-4、IL_5、IL_6、IL_7、IL-12等)、干擾素(如干擾素-Y )、巨噬細(xì)胞集落刺 激因子和腫瘤壞死因子。鋁鹽和MF59是適合可注射流感疫苗的優(yōu)選佐劑。細(xì)菌毒素和生物粘附劑是適合 粘膜遞送疫苗,例如鼻腔疫苗的優(yōu)選佐劑。本文所述的免疫原性組合物可與抗生素治療方案聯(lián)合給予。在一些實(shí)施方式中, 在給予本文所述的抗原或者包含一種或多種本文所述抗原的組合物之前給予抗生素。在一些實(shí)施方式中,在給予一種或多種本文所述的抗原或者包含一種或多種本文 所述抗原的組合物之后給予抗生素。適用于治療鏈球菌感染的抗生素的例子包括但不限 于青霉素或其衍生物或克林霉素等。本文所述的專(zhuān)利、專(zhuān)利申請(qǐng)、登錄號(hào)和出版物的內(nèi)容各自被納入本文作為參考。根據(jù)上述內(nèi)容,本領(lǐng)域技術(shù)人員可以作出除本文所述內(nèi)容之外的本發(fā)明的各種改 進(jìn)形式。這些改進(jìn)形式也落在所附實(shí)施方式的范圍內(nèi)。下面的實(shí)施例將進(jìn)一步闡述本發(fā)明, 這些實(shí)施例是為了說(shuō)明的目的,而不是為了限制本發(fā)明的范圍。實(shí)施例材料和方法肺炎鏈球菌染色體DNA提取在200mL液體培養(yǎng)基(THYE培養(yǎng)基)中培養(yǎng)表1所列肺炎鏈球菌,直到0D600達(dá) 到0. 25-0. 5。然后,在600RPM將樣品離心15-20分鐘(此時(shí)將一些團(tuán)塊保存于-20°C )。 然后在pH 8. 0用2. 7毫升50mM EDTA (最終體積3毫升)重懸這些團(tuán)塊,并轉(zhuǎn)移至15毫升 Falcon 管(馬薩諸塞州貝德福德的BD生物科技公司(BD Biosciences ;Bedford,ΜΑ))中。 將0. 55mL新鮮制備的溶菌酶(12mg/mL西格瑪(Sigma) L-6876,在50mM EDTA中pH 8. 0 (密 蘇里州圣路易斯的西格瑪-奧德里奇公司(Sigma-Aldrich Co. ;St. Louis,M0))和50 μ L 的5000U/mL變?nèi)芫?西格瑪M-9901)的水溶液相繼加入該Falcon管中。這些樣品在 37°C孵育1小時(shí)。孵育后,加入3. 6毫升細(xì)胞核裂解液(Wizard 基因組DNA純化試劑盒 (威斯康星州麥德森的普羅麥格公司(Promega Corp. ;Madison,WI)),翻轉(zhuǎn)六次混合樣品。 然后將樣品在80°C孵育5分鐘,再冷卻至室溫。然后加入18 μ LRNA酶溶液(Wizard 基 因組DNA純化試劑盒)并翻轉(zhuǎn)10次混合樣品。然后,這些樣品在37°C孵育30分鐘。
將每種樣品分入6個(gè)1. 2毫升的Eppendorf管。在每個(gè)Eppendorf管中加入0. 2 毫升蛋白沉淀液(Wizard 基因組DNA純化試劑盒)并翻轉(zhuǎn)10次進(jìn)行混合。翻轉(zhuǎn)10次后 立即將樣品在室溫下在Eppendorf離心機(jī)中全速離心30分鐘。然后將Eppendorf管的上 清液匯集到15毫升Falcon管(通?;厥占s8毫升)中。然后,加入0. 6體積的異丙醇,翻 轉(zhuǎn)10次混合樣品。將在火焰中加熱密封并彎曲的巴斯德吸管插入Falcon管并鉤住團(tuán)塊來(lái)回收沉淀 的DNA。然后用70%乙醇洗滌沉淀的DNA團(tuán)塊。最后,將沉淀的DNA團(tuán)塊溶解到3毫升 TEdOmM Tris HCl, ImM EDTA,pH 8.0)中。PCR 試驗(yàn)PCR的詳細(xì)內(nèi)容是本領(lǐng)域技術(shù)人員所熟知的。(參見(jiàn)Mark A.Valasek,M.A.,和 Repa, J. J. (2005) Advan. Physiol. Educ. 29,151-159 ;Ausubel, F. M. ,Brent, R. ,Kingston, R.E.,Moore, D. D.,Seidman,J. G.,Smith, J. Α.和 Struhl, K,《新編分子生物學(xué)方案》 (Current Protocols in Molecular Biology), Hoboken, NJ :Wiley, 2005.)。本文所用具 體參數(shù)如下(擴(kuò)增的最終體積為50 μ L) 基因組DNA的PCR擴(kuò)增翻5 μ L緩沖液(IOx濃縮液)0. 5 μ L BSA (0. 5mg/ml)1 μ L dNTP (IOmM 濃縮液)1· 5 μ L 寡核苷酸 OlOpmol/ μ L 濃度(15pmol)1· 5 μ L 寡核苷酸 OlOpmol/ μ L 濃度(15pmol)0.25 μ L Taq聚合酶(瑞士巴塞爾的豪夫-邁羅氏有限公司(F. Hoffmann-LaRoche Ltd ;Basel,Switzerland)。50ng 基因組 DNA加水至50 μ L
循環(huán)參數(shù)94°C保持3分鐘(一個(gè)循環(huán))94 V保持30秒,52 °C保持30秒,72 °C保持1分鐘20秒(6個(gè)循環(huán))94 V保持30秒,58 V保持30秒,72 °C保持1分鐘20秒(30個(gè)循環(huán))72 0C保持8分鐘(一個(gè)循環(huán))細(xì)菌(克隆)DNA的PCR擴(kuò)增 5 μ L緩沖液(IOx濃縮液)0. 5 μ L BSA (0. 5mg/ml)1 μ LdNTP (IOmM 濃縮液)1.5yL 寡核苷酸 @10pmol/yL濃度(15pmol)1· 5 μ L 寡核苷酸 OlOpmol/ μ L 濃度(15pmol)0.25 μ L Taq聚合酶(瑞士巴塞爾的豪夫-邁羅氏有限公司(F. Hoffmann-LaRoche Ltd ;Basel,Switzerland)。40. 25 μ L 7jC細(xì)菌循環(huán)參數(shù)94°C保持8分鐘(一個(gè)循環(huán))94 V保持30秒,52 °C保持30秒,72 °C保持1分鐘20秒(6個(gè)循環(huán))94 V保持30秒,58 V保持30秒,72 °C保持1分鐘20秒(30個(gè)循環(huán))72 0C保持8分鐘(一個(gè)循環(huán))DNA探針制備與雜交首先用單獨(dú)的容器平行制備DNA樣品(對(duì)于步驟1和2)進(jìn)行Cy3和Cy5標(biāo)記。(1)引物預(yù)先退火至DNA將1 μ g基因組DNA、2. 6 μ L隨機(jī)九聚物(英國(guó)白金漢郡的GE保健 公司(GEHealthcare ;Buckinghamshire, UK)(前身是安法瑪西亞制藥公司 (AmershamPharmacia))和1. 5 μ L摻入物(對(duì)照DNA)組合,加水至最終體積29. 5 μ L。將 該混合物加熱至70°C保持5分鐘,然后冷卻至室溫保持5分鐘。最后,短暫離心該混合物。(2)反應(yīng)將4mL NEB2 緩沖液、2mL 核苷酸混合物(2mM dATP, dGTP, dTTP 和 ImMdCTP)(各 自獲自英國(guó)白金漢郡的GE保健公司)和2mL dCTP Cy3 (或Cy5)(英國(guó)白金漢郡的GE保 健公司(GE Healthcare Buckinghamshire,UK)(前身是安瑪西亞制藥公司(Amersham Pharmacia))加入步驟(1)的混合物中。輕柔混合該混合物并加入2. 5mL DNA聚合酶I,大 (克列諾)片段(馬薩諸塞州伊維池的新英格蘭生物試驗(yàn)室(New England Biolabs, Inc.; Ipswich,ΜΑ) )0進(jìn)一步輕柔混合該組合物并在37°C孵育2. 5小時(shí)。最后,短暫離心該混合物。然后合并兩種標(biāo)記反應(yīng)液,使該溶液通過(guò)Qiaquick PCR凈化離心柱(加利福尼 亞州巴倫西亞的凱杰公司(Qiagen,Inc. ;Valencia, CA)以去除未摻合的核苷酸。用兩次 30 μ L的EB緩沖液從柱洗脫樣品。通過(guò)高速真空裝置(speed vacuum)將體積降至7. 5 μ L。(3)預(yù)雜交
鋁載玻片在5X SSC、50%甲酰胺、0. 2%505溶液中,421孵育2小時(shí)。然后在一個(gè) 培養(yǎng)皿中將載玻片浸入水中三次,在另一培養(yǎng)皿中再浸漬兩次。用氮?dú)獯蹈蛇@樣制備的載 玻片。(4)雜交將步驟2的DNA樣品在95°C加熱變性2分鐘。然后快速離心試管。制備包含1體 積緩沖液II和2體積100%甲酰胺(去離子化)的雜交混合液,將22. 5μ L該混合液加入 各個(gè)樣品中。然后混合樣品,短暫離心并在42°C孵育1小時(shí)。最后,在步驟3制備的載玻片 上加載樣品并在42 °C孵育過(guò)夜。(5)雜交后洗滌將步驟4制備的載玻片浸沒(méi)在55°C的IX SSC/0. 2% SDS溶液中(去除蓋玻片之 后)。然后取出載玻片并置于含相同溶液的第二托盤(pán)的支架內(nèi)。載玻片在軌道式振蕩器上 在第二托盤(pán)中室溫孵育5分鐘。然后,將支架和載玻片轉(zhuǎn)移到55°C的含有0. IX SSC/0.2% SDS溶液的第三托盤(pán)內(nèi)。將支架浸入第三托盤(pán)的溶液中5分鐘,然后在室溫下孵育10分鐘。 然后將支架轉(zhuǎn)移至含有與第三托盤(pán)相同溶液的第四托盤(pán)中,載玻片在第四托盤(pán)中同樣浸漬 5分鐘并在室溫下孵育5分鐘。然后將支架和載玻片轉(zhuǎn)移至55°C的含有0. IX SSC溶液的 第五托盤(pán),支架和載玻片在第五托盤(pán)中浸漬5分鐘。然后將支架轉(zhuǎn)移至含有與第五托盤(pán)相 同溶液的第六托盤(pán)中,載玻片在第六托盤(pán)中同樣浸漬5分鐘。最后,支架和載玻片轉(zhuǎn)移至含 水的第七 托盤(pán),支架和載玻片在第七托盤(pán)中快速浸漬兩次,然后用氮?dú)飧稍镏Ъ?。肺炎鏈球菌菌株基因組DNA的比較基因組雜交的微陣列數(shù)據(jù)分析方案載玻片獲取用微陣列掃描儀ScanArray (康涅狄格州舍而頓的帕金埃爾默生命分析科學(xué)公司 (PerkinElmer Life and Analytical Sciences ;Shelton, CT))以 10 μ m 的分辨率獲取兩 個(gè)雜交載玻片的彩色圖像。調(diào)節(jié)獲取參數(shù)(光電倍增管增益和激光器功率)以維持兩個(gè)熒 光團(tuán)通道間相當(dāng)?shù)臒晒馑?測(cè)定特定對(duì)照點(diǎn)的強(qiáng)度水平以及所有點(diǎn)的平均強(qiáng)度)。圖像分析用軟件Gen印ix 5. χ (加利福尼亞州日照谷的分子設(shè)備公司(Molecular DevicesCorp. ;Sunnyvale, CA))分析圖像。采用無(wú)益品質(zhì)點(diǎn)的自動(dòng)和手動(dòng)專(zhuān)業(yè)標(biāo)記程序 (curated flagging procedure) 0根據(jù)獲取的圖像,Gen印ix軟件提取微陣列載玻片上每 個(gè)特征點(diǎn)的強(qiáng)度水平并計(jì)算默認(rèn)統(tǒng)計(jì)參數(shù)。數(shù)據(jù)處理與質(zhì)量檢查通過(guò)本地安裝BASE(生物陣列軟件公司(BioArray Software Environment), rell. 2. 10,盧德大學(xué)(Lund University))進(jìn)行數(shù)據(jù)處理。數(shù)據(jù)分析包括兩個(gè)階段(a)背景校正和標(biāo)準(zhǔn)化在該步驟中,對(duì)每個(gè)點(diǎn)的強(qiáng)度減去局部背景強(qiáng)度。然后用 所有點(diǎn)的平均或中位強(qiáng)度標(biāo)準(zhǔn)化該強(qiáng)度。根據(jù)以下參數(shù),在BASE中采用背景校正和標(biāo)準(zhǔn)化 程序((插件rel. 1.4)實(shí)驗(yàn)標(biāo)準(zhǔn)化實(shí)驗(yàn)中位值實(shí)驗(yàn)背景局部背景校正閾值(bkg標(biāo)準(zhǔn)差)1新值(bkg標(biāo)準(zhǔn)差) 1
系統(tǒng)校正(CHI= CH2)有(b)數(shù)據(jù)合并-合并單個(gè)載玻片的重復(fù)點(diǎn)或重復(fù)載玻片的強(qiáng)度值,計(jì)算分離的兩 個(gè)顏色通道的平均強(qiáng)度。濾除標(biāo)記為低品質(zhì)水平或背景校正的點(diǎn)。該算法也評(píng)價(jià)具有兩個(gè) 顏色強(qiáng)度平均值之間不同強(qiáng)度水平的可能性(采用T檢驗(yàn),插件rel. 1. 7)。所得數(shù)據(jù)集合 儲(chǔ)存在BASE應(yīng)用中,可輸出用于其他分析。聚類(lèi)分析將兩個(gè)顏色強(qiáng)度水平的比率轉(zhuǎn)化為log2數(shù)值。計(jì)算的比率在數(shù)據(jù)集合表中列出,該表的列表示每個(gè)載玻片或合并的載玻片組 (實(shí)驗(yàn)),行表示每個(gè)點(diǎn)或組合并的點(diǎn)(基因)。將該表上傳到軟件TMeV (rel,3. LTIGR)中 進(jìn)行聚類(lèi)分析。采用三種主要的聚類(lèi)算法。(a)分級(jí)聚類(lèi)_該算法適合在不同實(shí)驗(yàn)中發(fā)現(xiàn)具有類(lèi)似存在/缺失圖案的基因類(lèi) 群。具體說(shuō),該算法采用以下參數(shù)設(shè)置樹(shù)狀選擇 基因樹(shù)和/或樣品樹(shù)距離米制選擇歐幾里德距離,皮爾森非中心連鎖方法選擇平均連鎖聚類(lèi)構(gòu)建相似性樹(shù)(基于算術(shù)平均算法的未加權(quán)對(duì)群方法,UPGMA)和相似性矩陣(基 于距離米制選擇)來(lái)代表實(shí)驗(yàn)之間和基因之間的圖形和數(shù)值距離。(b)巴氏模板匹配(Pavlidis template matching)-該算法適合發(fā)現(xiàn)存在/缺失 圖案類(lèi)似于模板圖案的基因。巴氏模板匹配適合在不同實(shí)驗(yàn)中發(fā)現(xiàn)圖案與參比基因相關(guān)或 不相關(guān)的基因。該算法適合在所得匹配和非匹配的組中采用閾值參數(shù)絕對(duì)值R(選擇與模 板相關(guān)或不相關(guān)的圖案),閾值P值0. 05,皮爾森默認(rèn)距離米制和各元素分級(jí)群聚。(c)微陣列重要性分析_該算法適合發(fā)現(xiàn)具有能夠?qū)?shí)驗(yàn)分成單獨(dú)的組的存在/ 缺失圖案的重要基因(定義如上文所述)。該算法適合發(fā)現(xiàn)給定實(shí)驗(yàn)組的特異性基因。該 算法采用以下參數(shù)統(tǒng)計(jì)學(xué)檢驗(yàn)不成對(duì)的兩組排列數(shù)目100SO:Tusher 等的方法Q 值無(wú)歸咎引擎(Imputation K-最鄰近歸咎engine)所得匹配和非匹配組中各元素的分級(jí)聚類(lèi)實(shí)施例1 檢測(cè)基因組DNA中是否存在菌毛I(xiàn)I島(INV104B)在純化的基因組DNA或直接在細(xì)菌上(集落PCR)測(cè)定是否存在表1所示肺炎鏈 球菌菌毛I(xiàn)I島(INV104B)。表2列出了用于擴(kuò)增的四種寡核苷酸。表2 PCR寡 核苷酸 采用以下PCR寡核苷酸組合,對(duì)表1所列各個(gè)菌株進(jìn)行三次診斷PCR 1008正 向-1009反向;1008正向-int反向;和int正向-1009反向。1008正向-int反向和int 正向-1009反向成功擴(kuò)增菌毛I(xiàn)I島(INV104B)的陽(yáng)性克隆。1008正向-1009反向成功擴(kuò) 增菌毛I(xiàn)I島(INV104B)的陰性菌株。在表1所示肺炎鏈球菌中檢測(cè)是否存在菌毛島,即rlrA島(相對(duì)于菌毛I(xiàn)I 島(INV104B))。類(lèi)似于菌毛I(xiàn)I島(INV104B),設(shè)計(jì)特異性引物,用于擴(kuò)增rlrA島的 指定區(qū)域。rlrA島檢測(cè)方法的例子參見(jiàn)2007年2月16日提交的題為“細(xì)菌抗原的純 化” ("Purification of Bacterial Antigen,,)的美國(guó)申請(qǐng)第 11/707,433 號(hào);和 2006 年 2月17日提交的題為“細(xì)菌抗原的純化”的美國(guó)臨時(shí)申請(qǐng)第60/774,450號(hào),這些參考文獻(xiàn) 的內(nèi)容被納入本文作為參考。表1指明許多肺炎鏈球菌菌株含有菌毛和菌毛I(xiàn)I島(INV104B)中的一個(gè)或二者。實(shí)施例2 :23F、INV200 和 0XC141 的序列1.序列下載與組裝從Sanger網(wǎng)站下載四種肺炎鏈球菌菌株的初始序列(參見(jiàn)萬(wàn)維網(wǎng)“Sanger. ac. uk/Proiects/Microbes/,,)。Sanger序列由不同數(shù)量的非重疊毗連群組成。下載序列 的詳細(xì)情況在表3中列出表3.下載序列 為鑒定毗連群的可能順序,采用MUMmer3. 19將該序列與TIGR4完整序列進(jìn)行比 對(duì),以形成單個(gè)假分子。為分離兩個(gè)隨后的毗連群,插入以下序列NNNNNCATTCCATTCATTAATTAATTAATGAATGAATGNNNNN (SEQID NO 28)SEQ ID NO :28設(shè)計(jì)成(i)在所有六個(gè)讀碼框內(nèi)產(chǎn)生終止密碼子,從而預(yù)測(cè)所有基 因均未跨過(guò)接合處,和(ii)在所有讀碼框中提供起始位點(diǎn),指向毗連群以預(yù)測(cè)在其末端的 不完整基因。將沒(méi)有對(duì)齊TIGR4基因組的毗連群設(shè)置在假染色體的末端。2.基因預(yù)測(cè)用glimmerf. 02套件預(yù)測(cè)基因。用TIGR4預(yù)測(cè)基因作為訓(xùn)練集來(lái)訓(xùn)練隱馬爾可夫 模型(Hidden Markov Model)。3.蛋白質(zhì)集合比較采用Fasta將每個(gè)基因組的所有蛋白質(zhì)與其他基因組的所有蛋白質(zhì)進(jìn)行比較。如 果其氨基酸序列在其長(zhǎng)度至少50%上的相同性百分?jǐn)?shù)至少為90%,則認(rèn)為該蛋白質(zhì)是保 守的。不符合該標(biāo)準(zhǔn)的0XC141、INV200和23F的氨基酸序列如下所示。這些序列可提供 適合本發(fā)明組合物或治療方法、用于診斷肺炎鏈球菌感染和免疫對(duì)抗肺炎鏈球菌感染的多 肽和/或蛋白質(zhì)。4.起始密碼子本文所示氨基酸序列的N末端殘基表示對(duì)應(yīng)核苷酸序列中第一個(gè)密碼子編碼的 氨基酸。在第一個(gè)密碼子不是ATG的序列中,應(yīng)理解當(dāng)某密碼子是啟動(dòng)密碼子時(shí)它應(yīng)被 翻譯為甲硫氨酸,但如果該序列位于融合伴侶的C末端,則該密碼子可被翻譯成所示的 非-Met氨基酸。所示序列特別公開(kāi)和包括用N-末端甲硫氨酸殘基(如甲?;?甲硫氨酸 殘基)替代任何所示非-Met殘基的所列各氨基酸序列。5由0XC141鑒定的序列>orf00007MEMSFIAQDFDKLNIITVLESRTQAIIRNPMNTRLSSDTESSFNKIVRN (SEQID NO 29)>orf00009MELAETSIVKKNHQIPCIINQKIAQKLIKKTSMTDIDHQLSISTSTVIRKINDFHFEHDFSRLPEIMS( SEQID NO 30)>orf00013LFKIGRVYYRQLQEDLLTCCNKYPKLFFFIIISLNSTQSGGVF (SEQ ID NO 31)>orf00015MKYNKTKYPNIYYYETAKGKRYYVRRSFFFRGKKREKSKSGFTTLPQARAALVELEQQIQEQELGINTN LTLDQYWDIYSEKRLSTGRWNDTSYYLNDNLYNNHIKAKFGSILLKNLDRNEYELFIAEKLQNHTRYTVQTLNSSFM ALLNDAVKNGNLLSNRLKGVFIGQSDIPAANKKVTLKEFKTWIAKAEEIMPKQFYALTYLTIFGLRRGEVFGLRPMD ITQNDSGRAILHLRDSRSNQTLKGKGGLKTKDSERYVCLDDIGTDLIYYLIAEASKIKRKLGIIKEQHKDYITINEK GGLINPNQLNRNFNLVNEATGLHVTPHMMRHFFTTQSIIAGVPLEQLSQALGHTKVYMTDRYNQVEDELAEATTDLFLSHIR(SEQ ID NO 32)
>orf00016MSYSYVALDVETANDFRGSVCSIGLVKFKDGNIVDTFYTLINPEEEFDDFNIFIHGITPEDVLDSPTF PEVRKSIVDFIGLDIVVAHFAQFDMGALKDVYQKYELDFDNIEYICSYRLAKVALPGQLNYKLKRLAKNLNIELDH HNALSDARASGLILEYLLSTNSFSDLTAFLKEYRYNKTGLLGQYGFKRKKGYQYKENLIYQPTEEEKAAMNPDHY FYGLYFCFTGKLERMTRKEANKAAALVGGIPEKGVTKHTNILVVGEQDWRVVGTDGLSSKMKKAQTLLEKGQDIE IMTENDFIRLLEE (SEQ ID NO 33)>orf00017MSLLSLHQCKVFLFYHDFISHGFKIVVGHEFEVIKLCGVIQAF (SEQ ID NO 34)>orf00019MKNKKPNAERLQEIADYFNVSTDYLLGRTDNPAIA⑶SKEYTWQGKTLNVEEMASNVMMFGGRELTDEK KKIIQSIIEGYLKEAGD (SEQ ID NO 35)>orf00020MSKLTKEDVLQVSQEIINDAIPVIKDMLDEVFKEYPIDMEIRKAILNSVLVAHKLSTETTVSLLTELVN AQEN (SEQ ID NO 36)>orf00021MSKELKIIKAKIKTRLIELDMTQAELAKQVSVASSVISELLKYGKGSESVKEKVADVLGIENPWENS (SEQ ID NO 37)>orf00022MDYQILIQPAISVILAIISGLffSYIASKANNKAEIEKQAKEHSHIVEKLEKEFHYQIDTLKQQHTLE LEKVKQAHELRLQELEKVSQIDTETDKAMKMNDLIYKTFTGEVDLDKALKLADKANNHKQKLNKKFIQKTSKKS (SEQ ID NO 38)>orf00023MNEIFNFHGQEVRTLTIDDEPWFVGKDVADILGYSKARNAITLHVDEEDALKQGIPTSGGTQDMLIINE SGLYSLILSSKLPQAKEFKRWVTSEVLPAIRKQGGFIREDLDEDAFIALFTGQKKLREQQATMLEDIDYLKSEQPIH PSYAQSLLKKRKARVVACLGGIDSPAYADKVFAQSVFRQAEIDFKDHFNISRYDLLPKKHADAALAYWMTWEPSTNT KMKIMKLNSFDDV (SEQ ID NO 39)>orf00025MFEPPILDQLMGVGALLLGFAGACRHIKLQEQRKEEERREEQEFASMIIQGYNHAYERGREAERQEIRK NIRRPFKGFTYDNEPPQGLRPEPLALPEPKQSAIRLL (SEQ ID NO 40)>orf00026MEELIESLDNLIMIVKELEGRESTSRHFITIffENDYKNLLLVKEYLTDYEKLAKDYRYVTLKNKLLKIE KMELEGRHIYEDMRMKYRANRRKffGARYV (SEQ ID NO 41)>orf00027VLGMSEIKWIKITTDIFDDEKICLIDALPDPDAILVIWFKILTLAGKHNSNGLLMMTDKVHYTDEMLAT IFRRPLNTVRMAIGVFEQFGMIEIIDGIISLPNWEKHQNVDGMEKIKEQTRNRVAKYRKKQKNLALGNVTGNVTVTD GNALEEDKDKNKNRLDKDKNKKRITTTSSGSEENILELFQSEFRRLLSGFEIEEINHLLNENDVDLVKEALKTAINS GKPNIKYIGGILRNWQMNNVTTVEQVRQSEKKNKDKKEEQEAKDEWGY (SEQ ID NO 42)>orf00029
MRRSASMVDNVFEEIALSYRRNTEQQEEFCEKHNIPLIKILRTESVVCRMCESERIHEENQERVNELAN AENERERKYYLEKFSLYDEVLKNATLDNFETPTEKEAEKLAFAKRICREWSEGARNNIVLQGEAGTGKSHLAFAMVK VLSEYTKEIAIFINVTDLLMKIKADFSQEEFLVNKIASAKFLVLDDLGMEKDSEWSFTILYNILNKRSNTIITTNLI SADIQKRYGRPFMSRLMKGVDKDHLMVFNDLTNKRKQYF (SEQ ID NO 43)>orf00030MLELYFVYNGHCKFFLGRFDNVDDLIEQMEDHQWAFSAITHPRFQKHIGQRTTRFDYGSKDCYYLATFS GGE (SEQ ID NO 44)>orf00031MVGVTYQEIHLFVEFLKEQYGQGRPDYIEALNDLDGLVEVSYREAIERFLEDEVR (SEQ ID NO 45)>orf00032MMEELKKKVNAVYNWTVEDGKPQPPQQDLPQAVKDRVDYFffEMAEDGMTFMGAMECIFADEKPTDYELG ATKGWLPKSKEFDDWIGYSPSMAQVVIAVYLIYGGN (SEQ ID NO 46)>orf00033MEETKMNKQELlKKLEERRTlIGNFQGYAVSYFffIYffIVEK (SEQ ID NO 47)>orf00035MEFVSPIKDNDDIQAMKDYLREffNEMYYMLFITGLNTGLRVCiDILTLKVKDVQGWHIKLRERKTGKQIT RRMTKELKKEMRRYVEGKPFHHFLFKSRQGQNKAITRERAYQIIHEAAEELGIDNVGTHTMRKTFGYKYYNKTKDVG TLQKMFNHSSPAITLRYIGIEQAELDDALRNFVI(SEQ ID NO 48)>orf00036MYNKPVRPSLKSKKWEKFRDRIMRKHDYLCQESLRYGISVQAEMVHHIFPVSEYPELEFVEWNCLPLTN KKHNTFHDRVNDRVINQGLYffQKKRKKEFLNFFKNEK (SEQ ID NO 49)>orf00037LAKPITAKSIKSKVVKQMKDLGTYRKEFEMIIDIFAGMLYQYQKLAQDYANLGYPVTDTYVNKAGAENE RKVPILTAMEILRKDILSYSNQLMMNPKSLGEVVEQE⑶SVLTEVLKFKNEIKKKRVSGNG (SEQ ID NO 50)>orf00040MGNLDKAKEYAQHVLTHREEHCEENILAAERFFRDLENPAFEMDEDMVDFVIHFIENVIVHQQ⑶DMFA VSIRNKPLLLQPWQHFVVVNLFGFYYKGTNERRFKEALIMLARKNGKTSFTAAIALAYQILDTDSGSKCYIVANSVK QAMEAFGFLRFNVERWNDKNIRIKDNNQEHSITANF⑶EGSFFIQALANDESRLDSLNGNVIILDEAHTMRNSKKHG LMKKTMSAYRNSMLFVISTAGDIPTGFLANRLKYCQKVLKQLVTDDSFFIFICKANQSAD⑶WNYLDENILKMANP SWGVTVSLKALKEEAEQAMNDPQTRNEFFNKTLNIFTNSMNAYFNPDEFIASDSCYDWSLEELARLPIRWYGGADLS RLHDLTAAALYGVYHDGEKDVDICITHAFFPRINAQKKANDDGIPLFGWQSDGWLTMSNTPTVLYDDIVKWFIKMRE KGFKIAAVGMDRKFGREFLTKMKQARFKMIDQPQLFYLKSEGFRRIEFKVKNKEFYYLHSDAYEYCVSNVRAIEKVD DAVQYEKLD⑶GGTARIDLFDASVFACIQALANLGKG⑶VMRFFD (SEQ ID NO 51)>orf00043MNEIVLSEHEINLLINKGRVKVILNGEVVTIRQRHMKNLMAETVKWEKQVIDVSQNIVRNKHFDSLFQNTFR (SEQ ID NO 52)>orf00045MGIFEKFWKRNKPSKPINMLSHSDLGLSNLMDSYVPLARNPDVVTAVNKIADLVS匪TIHLMENTDKGDIRIRDGLARKIDINPCKHMTRKSWIFKIVRDLLLY⑶GNSVLHVEYEPVTDYISNLRPFPMREVSFQTDKDSYVISF RGEEYSPDEVVHFVINPDPDILYIGTGFRVTLTDVVQSLNMATKTKKSFMNGKNIPSLIVKVDSSSAELDSEQGRER IAEKYLSTSRVGAPWIVPEALLDIQQVKPLSLTDIALNESVELDKRTVAGLLGVPAFILGVGEFNKTEYNNFVNTTV MSIATTITQTLTRDLLLSSNRYFKLNPRSLFSYNITELSAVAQQMANSAAMRRNEWRDWLGMAPDPEMEELIVLENF LPQEKLGDQNKLKGGEEENAKAK (SEQ ID NO 53)>orf00047
MQKRNSYRATQFQTREEESGDLVLSGYFIKFDEETELWRGYHEVIKRAGVEKAVTDADIRALFNHDDSL VLGRTGNGTLTLGVDDVGLFGDIIINKDDPQAVGAYARVKR⑶VIGCSFGFIPVKIETEEREDGSYLDTVLELEIFE VSPCTFPAYPQTEIAARQKDFESQKRANREALDKRKKEIKEKFKL (SEQ ID NO 54)>orf00048MNKALIFGARMRAKATKVVELEETIEELNKRSVVELEKLDRAKNDEEVLAVEKTVDGLQREIEEKEAEK VQLENEIDELDKQIKEQNRKAPTPGKMEERGGKTLGQREAFNHYLRTKEARADGFKSAEGEAIIPVELMTPKEAKQD KTDLTSLVNIVNVKNASGKWSVVKLTDQAMNTVEELEENPELAKPTFTKVNYEIKTRRGHLPVSQEFIDDADYDVMG LVAKQTKNQERITKNKEIAKVLKTATSKSAAGLDGLKDILNVELKTYYNATIVCTQSMFAALDKIKDKDGRYMLQTD ITSPTGYKFAGRVIVVYPDDIIGESKGDLKAFIGDVGEFATLFDRAQTTVKWQDDKIYGQYLATANRFDVVKVD⑶A GFYVTYTDAVL (SEQ ID NO 55)>orf00050LMNVEDKDMSKDDTLTTEVEKEETKVVDGKPEEGDEE (SEQ ID NO 56)>orf00051MDNVQLLELLKLKLGIATKLRDKPLEKIIEAVKTELEDNLGVLLDLDSSEDQMFVVDFAAFRYEGGVDM PRHLQffRLHNLQIASKKKVKNVES (SEQ ID NO 57)>orf00052MWNHEIKLISKKITGKDKLLQPISEDVEVTLLCRKKNVTRSEFYQANQAGLKPSLVVEIRNFEYENQEF AKFEGKQYRILKTYPIDSEILELTLTEVLK (SEQ ID NO 58)>orf00054MSNDLADLIAKELAAYSDEVTEEVDKIAEQVTDETVDELKETSPKRYGKYRRSWKKKKLANGSFVVFNA VASLTHILENGHLSRNGGRVAGIVHIKPAEEKAIQNFEKRIKEIGK (SEQ ID NO 59)>orf00055MKLSDFAAILEQANLPVTYRAFKIGNAPDLPYLVYYESSPVINSADNTVNHQIKSVTVELAFESKDEDL EERLEELffANHKLFFEVQEETFIETERLYVKSYTVYLY (SEQ ID NO 60)>orf00057MTQENKVTFGLENVHIAPIKTLAADGVITY⑶VFRFPGAMELILDTKGETTPIKADNKNYHFMNSNEGY EGKLKIPHIIDEFATKILGEIKDPQTGVMTEKADASLTEFAIMFQFEGDKNKTRYVMYYCFASRPSLGSKTKNGTST NERELSFKASPRPLDTVVKRSITSADDKDAYDNWFKKVYEPTAVAA (SEQ ID NO 61)
>orf00058MRKIVLV⑶QEYELGTNGYTPIAYKQQFGKDYFQDLFSMLKNQSFMNELNKLETDKELTATNIDISMLS DFDMTFFNRLFffTFAKSANPQIKPYEQFFMEMEIFPIQEVGPVLMEMLNASMTTKKHQMNQNQLAKKSSQ (SEQ ID NO 62)>orf00060
MAGNIKGIKIEIDGDTQPLQKALKAINKESVNTTNELKQIDKALKFDTGNVILLTQKQEVLQKQIGITR DKLETLRQAQSKVDEEFKKGNIGSEQYRAFQREVEVTQNVLKGYEGKLASLTQALEGNGDAAKNNQAQLKELQNEQK LLASESEKVVSSFKLQESQMGANASEADKLALAEKKIGAQSEIVTRQIENLEKQLSLTKEQYGENSAEANKMEAELN QAKTAYANLNQELGKLGSTAKSNQTQLKELQNEQSQLASEMSKVTSSFKLQESALGSNASEAERNALAQKKIGAQSE IVSKQISNLEQQLEITKKEFGENSTQANKMESELNQAKTAFNHLNDEMKGTKSAADSTQESLSEISRNLRAELLQQF SEKLSAISEKLVEVGKEALEAAAQMQASNAQFTTVF⑶METQAREALNAIGQEMDIVPERLQGSFTQMASFAKTSGL DTAEALDLTSRATRAAADGAAFYDKSIESVTESLQSFLKGNFANDAALGISATETTRNAAANKLYGKSFKDLSEAQK QLTLLQMVEDGNKLSGALGQAARESDGLENVMGNLKQAGTNALSAIGQPLLEMMIPVFQTLATIVKGVAELFSSLPA PVKDFVVILGTVVTAVGVIAPIFLSLQALAEFLKISIGEMIIAALPIIGTAIAIAAAVAAIVAIVKYLWETNEGFRD AVTTVffNAILEVINAVVSEISNFVMSIFGTVVTffffTENQELIRTSAETVWNAIYTVISTILDILGPLLQAGWDNIQL IITTTffEIIKIVVETAINVVLGVIQAVMQIITGDWSGAWETIKGVFSTVffQAIQSIVQTIFSAIQSYISNILNGISG TVSNIWNSIKDTVSNVLNAISSTVSSVWEGIKSTISSAINGARDAVSSAIEAIKGLFNFNISWPHIPLPHFYVSGSA NPLDWLSQGVPSIGIEWYAKGGIMTKPTIFGMNGNNIMVGGEAGNEAVLPLNDKTLGAIGRGIAQTMGGTSPTINIT ITGNTVREEADISRIADEVAQRIADELQRKTQLRGGFT (SEQ ID NO 63)>orf00064MIKHNELVIDGVRTSSFPFKVIVHDSPSIALGESKTALLEHGGISGAIVQTNKHRELVKKTYTIYLVKP TEEQMNQFMSLFIREKFWLESERVKTTRLWCYKVNVSDLEEVQPGLYMTKATFTCHPTKHFKVTDTQRLTRSGTLNV QGSALAFPKITIVGQSASETSFTIAGQVIRLERLTESLVMVNNPDNPSFKTTTGKPVKWSGDFITVDPAKVKNIGVV LGPGIQSLEIETVffGffA(SEQ ID NO 64)>orf00068LLYLLNEDVRTVRWNGESLHEATSAIVKETMNGDFTLTVKYPISDSGIYQLIQEDMLIKAPTPVLGAQL FRIKKPVEHNDHLEITAYHISDDVMQRSITQMSVTSQSCGMALSRMVQNTKTALGDFSFNSDIQDRRTFNTTETETL YSVLLDGKHSIVGTWEGELVRDNFAMTVKKSRGENRGVVITTHKNLKDYQRTKNSQNVVTRIHAKSTFKPEGAEKET TIRVTVDSPLINSYPYINEKEYENNNAKTVEELQKWAQSKFSNEGIDKVSDAIKIEAYELDGQVVHMGDTVNLKSWK HNVDAFKKAIAYEFDALKEEYISLTFDDKAGIGGSRASGGLSSAADAILGVTESAQEIALEKALQNADLDFDHKAGL LRQEISDDIELAKARAEEVKRELSDTINQRFNSFDNGPLKETKRKAEEALRNAGASSSLAQESKRIGLDSVARLEAF KSQTTSAQTALS⑶LDALKRTIANDIRPKQAQAEAEIAKQVEALSRTKNELAGASTLLAQEAKRIELDSVARLEAFK SQTTSAQTALSGDLDALKRTIANDIRPKQAQAEAEIAKQVEALSRTKNELAGASTLLAQEAKRIELDSVARLEAFKS QTTSAQTALSGDLDALKRTIVNDIRPKQAQAEAEIAKQVEALSRTKNELAGVKSAQATYKETTTRRLSELTNLANGK ASKSELTQTAEELSSKIASVQASGRNLFLNSLFKQDIPKTGIWTTSTYTATIDSESKYLGHKALKIIGLNPSGRDGG NPKVTYPALGQFGKVIPGSTTNQDVTISFYAKANKNGIMLRSRLGNIGYKTGNVTLSTEIKRYAVHIPKGWTNESKR TTNEWLFNFNQEGTVWIWMPKFEISDVDTSYSEAPEDIEGQISTVESTFKQRANSLEAGVSRLTEGLRTKADISSLN VTAENIRQSVKSLETDTQNKLNQKLSQAEFEVRAGSIRQEILNATKDKADKTLVVSEAGKLREEFSKMKVGGRNLffI KSKTVGAVIEKLPENHVTGQKECYRLENNSTLTFNLEPDFSSRLYQKVTFSAWIKYENVVQGRNFWNVFNCFKHYLF RKNSETGVQSGPDYDTLGRYKGSADWKYITFTYDYSEKTNFDQLKTLLRFNLEGATSGTAWVTGIKVEIGSVATDWS PAPEDADGLITEAKATFERTAQGLRTDLSAITEGLRTKVDISALNVTAENIRQSVKSLETDTQNKLNQKLSQAEFEV RAGSIRQEILNATKDKADKTLVVSEAGKLREEFSKMKVGGRNLWIKSKTVGAVIEKLPENHVTGQKECYRLENNSTL TFNLEPDFSSRLYQKVTFSAWIKYENVVQGRNFWNVFNCFKHYLFRKNSETGVQSGPDYDTLGRYKGSADWKYITFT YDYSEKTNFDQLKTSLRFNLEGATSGTAWVTGIKVEIGSVATDWSPAPEDADGLITEAKATFERTAQGLRTDLSAIQEYVNKDGQRQEALQRYTREESTRQATAVRELVNRDFVGKATYQEDVKGINQRIEAVKTSANKDIASQIASYRQSVDG KFTDISSQITTYKQDVGGQISGLSNRLTSSEQGTTTQISNLSNRINSNKQGTDNQISNLKTQVATNKDNAERQMGRI SDQVSANKANADSQFANVTNQLARKVETTDFQRVKETSKLYERILGNTENGIADKVARMALTNQLFQVEVAKNASNG QNLLKGTKDFSGGWKNKGANWKKHAEKYKGVDVLFKNNSWNGVGQEIDAKIGEVYTFSLWMKSDWKNDTVNFYVNRN GSVEKGWGVPSETSVAITSEWKRYSFAFKITVDGFIFPRVERLNQNTNLYIAGLKLEKGSYATPYTEAPEDTDEAIR SVQSQLTGSWAVQNINSAGDIISGINLGANGHNRFVGKLTHITGETLIDRAVIKSAMVDKLKTANFEAGSVTTTILD AEAVTADKVRFDAAFIRKMTANDAFIDQLTSKRIFSTKVESVISSSTFLEAYQGRIGGFTIGRFAQGRGRWISGINQ FSVGMGNGEGGSYNGENTAFWANWGHSWNSPGPNAWYVTTSGNMYCRNGADFHGKVDFSNSSRANFYGNTTFSRSPV FSNGIELGSKDVLGDGffNPKGGRNAVVWWNQVGSGSVKYWMEQKSDRRLKENITDTAVKALDKINRLRMVAFDFIE NKKHEEIGLIAQEAETIVPRIVSRDPENPDGYLHIDYTALVPYLIKAIQELNQKIEKMEKTIA (SEQ ID NO 65)>orf00069MNTEQLNQALQMTIREMSTTSTNSMITSNILSIQLNEQREENQRLQARVDELEALLDEQTKPADKGE (SEQ ID NO 66)>orf00071MAETIQNTDNLLDLTKITEPFDLASALRYMKENGEFIRCKNVSDDFYMYRDVQKRPVIVNGRRQFKDIE TVWAFNQWGGTITTINVAVLLNHEFYIMKFDAEGNPDWTNPTVEPKE (SEQ ID NO 67)>orf00072MQIEFFNFLRSVVQTEDGLVLYALALIVSMEIIDFVTGH (SEQ ID NO 68)>orf00073MILIPASVLLPEKTGFVFLHSIYLGYIAFTFQSLIENYRKLKGNVTLFQPIVKVFQRLLEKDDDTKKGE (SEQ ID NO 69)>orf00074MQQITEIITNGAISILVILAGIAVKAVKEYLVKKGGEKTIKIVEILAKNAVNAVEQVAAETGYK⑶EKL AQARAKVRAELTKYNISMTDKDLDTFVESAVKQMNDAffKGR (SEQ ID NO 70)>orf00075MAFNQFNRCVTLSIPTAPNIPTSWHRTYLHDTAVSD匪(SEQ ID NO 71)>orf00079MKNREEEffQGIIAKNAILLIIAPFYFLIIVKNGVLLKIKTVTEITAF (SEQ ID NO 72)>orf00085VEEVEVAEVKNARVSLTGEKTKPMKLAEVTSINVNRTKTEMEEFTRVLGGGVVPGSLVLIGGDPGIGKS TLLLQVSTQLSQVGTVLYVSGEESAQQIKLRAERLGDIDSEFYLYAETWQSVRAEVERIQPDFLIIDSIQTIMSPE ISGVQGSVSQVREVTAELMQLAKTNNIAIFIVGHVTKEGTLAGPRMLEHMVDTVLYFEGERHHTFRILRAVKNRFGS TNEIGIFEMQSGGLVEVLNPSQVFLEERLDGATGSSIVVTMEGTRPILAEVQALVTPTMFGNAKRTTTGLDFNRASL IMAVLEKRAGLLLQNQDAYLKSAGGVKLDEPAIDLAVAVAIASIYKDKPTNPQECFVGELGLTGEIRRVNRIEQRIN EAAKLGFTKIYVPKNSLTGITLPKEIQVIGVTTIQEVLKKVFA(SEQ ID NO 73)
>orf00088MGVSIFLALFYMIPALYFLFHIGKKWELPKKVLILSLLGAICSFTSLLLFGIYNHRRKSSKV (SEQ ID NO 74)
>orf00094VFVALVSITFSLTNFFKILINLTAQVSPQVIDEKILMMDLNLNNYLSTVIQLRQDVYTGIKILH (SEQ ID NO 75)>orf00095VNIASLQNGHIFCWQVQHIANKLTSDFWIAEYFLSNQIISWADARMSENPPIPPSIVS (SEQ ID NO 76)>orf00103MKIKEQTRKLAAGCSKHCFKVVNGTDEVSSKHCFEVVDGTDEVSSKHCFEVVDRTDEVSNHIYGKATLT WFEEIFEEYKSLHNKTHITKVV (SEQ ID NO 77)>orf00109
MNDDDSRCIHIERDGKTIEFGYLNISSTDRNTSHADGLVGIFNSNFSGVRVRGIAVFLNGPDNLDTTLV GNFQTIffNFRIICIHSQNTCNKG (SEQ ID NO 78)>orf00110LEFNFCRSIIKNGRDNLPNTNSTSGMATRWANHNWSDDIKDRLKTK (SEQ ID NO 79)>orf00114MRYDFGKVYKEIRESKGLTQEEVCGNVISRTSLSKIESGKATPKYENMEFLLRQINMSF(SEQ ID NO 80)>orf00116MNYNLKYLLSGIFVLVFIGFLVWMRYFNQRKEEEHSDVSFEARLDSEVKTLYKQLGLGEEPHYFLAYRY LHPWFDLAILPPTVEIFLTKIALVMVTPDELLIRNLGNGLTFTSEHHRDLRQGLIRIPKSEMKEFEIRNWKKFFVFG DFLTIKTSQHSYYLQVRDDGLQKGSLSTKHFSDLKSQDFLGLLTDKRTF (SEQ ID NO 81)>orf00124LSLLDLRGSLCLRIYLHEPLITTVSQDFTSLSDISHF (SEQ ID NO 82)>orf00125MDFKSFIIGLVVGIFGPYMDDLIRKKFLKSSEKKTEKSVKK (SEQ ID NO 83)>orf00175MGRFILFENLFKPGQLHLAVDMVTDFVSSIHNLKTVF (SEQ ID NO 84)>orf00177METSISMADFYGKYQNENLELIDVREAHEFQAGHAPGAKNLPLSTLEQGYKELKPDHEYYVICQGGVRS ASTCQFLSSQGLTVTNVEGGMNVWPGQVE (SEQ ID NO 85)>orf00179LGGKSCLLEDRLCDIAAQTTVAADDVGLFFVQFISFLLDTLSVFDTIVQN (SEQ ID NO 86)>orf00183MKIKDQTRKLAAGCSKHCFEVVDRTDEVSSKHCFEVADRTDEVSNIYTARRR (SEQ ID NO 87)>orf00184MKLLSIAISSYNAAAYLHYCVESLVIGGEQVGILIINDGSQDQTQEIAECLASKYPNIVRAIYQENKGH GGVVNRGLAEASGRYFKVVDSDDWWILVPT (SEQ ID NO 88)>orf00185LKILETLQELESKGQEMDVFVTNFVYEKEGQSRKKSMSYESVLPVRQIFGWDQVGNFSKGQYIMMHSLIYRTDLLRASQF (SEQ ID NO 89)>orf00186 MYYLPVDFYRYLIGREDQSVNEQVMIKCIDQQLKVNRLLVDQLDLSQVSHPKMREYLLNHIEITTVISS TLLNRSETAEHLAKKRQLWTYIQQENPEVFQAIRKTMLSRLTKHSVLPDRKLSNVVYQITKSVYGFN (SEQ ID NO 90)>orf00194MSLQIKLKKLAKELSKLLKDSNLETVDKDVLENSQEELQKAVLFLADEKGSEHTAAELIDNLKEVIAKL KANA (SEQ ID NO 91)>orf00202MKIKEQTRKLAAGCSKHCFEVVDKTDEVSYIYLRQGEADAV (SEQ ID NO 92)>orf00213MSKEKVILAYSGGLDTSVAITWLKKDYDVVSVCMDVGEGKDLDFIHDKALKVGAVESYVIDVKDEFATD YVLVALQSHAYYEQKYPLVSALSRPLISKKLVEIAHQTGATTIAHGCTGKGNDQVEYQIAVAKKANEAKK (SEQ ID NO 93)>orf00215VLDSLVFMGFSMKLIHDLDTHTTHSTAKMLYNVKAIKNDFSIRE (SEQ ID NO 94)>orf00218MGQLHFITKLLDIKDTNTQII DVVNRDSHKEIIAKLDYEAPSCPECRSQMKKYYFQKPSKIPYLETTG MPTRILLRKRRFKCYHCSKMMVAETSIVKKNHQIPRIINQKIAQKLIEKISMTDIAHQLSISTSTVIRKLNDFHFEC NFRNLPKIMSWDVETVRGVTVSIGRWR (SEQ ID NO 95)>orf00220MRYDFGKVYKEIRESKGLTQEEVCGGVLSRTSLSKIESGKTTPKYENMEFLLRQI匪SFEEFEYICHLY QPSQRTEIMQTYLNMTSIIGSNSLVHFFETCQDYLKTHHDLPIEEIRDMLEVVIYIRQHGAGELSDHAEQVVKKLWR KIEKQDTWYESDLKILNTILFSFPIEYLHLITGKILQRLEVYKNYQHLYDLRIAILLNLSTLYLYNQDK匪CKQICY TLLEDAKNKKSYDRLAICYVRIGICTDNAKLIQKGFSLLELTEETSMLSHLKKEVETHYQPKKL (SEQ ID NO
96)>orf00221MNSKELSISMLKKYPCTMQHDQSDCAAAVVSTVLLSYKKELSIMKIREIIGTDMYGTTVSGIVSGLNKL NFTVKAVRVALEDLTPKLTFPAILQVKNDLGQNHFVVLHSIKRNSKFYVADPASGIRKMSSDELGEIYQGITLFMVP NSDFERGKLKGKGLLDLFGRLIFNQKGLISTVILASFVLSIIGILSSLFSKVIMDEVIPYALKNSLYMFLIVFGIVS FLQTLLSAFRQHVLLFLSRKIDIPVLMGYYDHIIHLPYSFFGSRRVGDVLTRFQDAMTIKNVFTSVSISLVMDITLS VISAVVLWTINQSLFLILVFMVIVNIILIYCFKKPYKKINHEQMEANGLLNSQLIESIRNIDTIKSQHDEEQRLNKI EEKFVHTLEIGYKEGVLQNIQSTISSMTSTMGGLLFMGVGALFIIDGKMTI⑶LLVFQTLSQYFTEPIQNLVGLQLT FQEVQVAVSRLQELMEVDREDIALDYSIRDFTLCDDIEFKDVTFAYGSRPPVIKDFNLRIKQGEKIAFVGESGAGKS TLVRLLLRFINPSEGKIRIGENDLSDLDYGKLRKKISYIPQTIELFTGTIIDNLKIGNPSVTYEDMVRVCRIVGIHD TIQRLQNRYGSFVEEGGQNFSGGEKQRLAIARALLSKADLYIFDEATSNLDSFSEQIIQDLIFNKIMDKTTIVVAHR LSTILRCDKICFLENGTIVEYGTHEELMAKNGKYARMVGLQSVQVNQQIQSQAVLDTEEVTYG (SEQ ID NO
97)>orf00222
MAKLEVKDNKKLVLKSVICKKLHDTKVEDVDQEINKFHQHLQLLKAQIFGPLIVKSCGTTIHDDGLIT TDFEFYIQAHNAQQYSNIYDVQDSISVPYCLYVRFEDSPEYLQYAYSKLDLYVYENDIQTDGIVYTVYVNSSPEKM VVDIFRPIVSL (SEQ ID NO 98)>orf00223MKLYNKSELRYSRIFFDKRPPAFAFILIISTAIILSGALVGAAYIPKNYIVKANGNSVITGTEFLSAI GSGKVVTLHKSE⑶MVNA⑶VIISLSSGQEGLQASSLNKQLEKLRAKEAIFQKFEQSLNEKYNHLSNSGEEQEYYG KVEYYLSQLNSENYNNGTQYSKIQDEYTKLNKITAERNQLDADLQTLQNELIQLQQQ⑶SSSLSDTTSDDDKAKLET KISEITTKIEALKTNITSKNSEIDSQQSNIKDMNRTYNDPTSQAYNIYAQLISELGTARSNNNKSITELEANLGVAT gqdkahsilasnegtlhylvplkqgmsiqqgqtiaevsgkekgyyveafvlasdisrvskgakvdvaitgvnsqky GTLKGQVRQIDSGTISQETKEGNISLYKVMIELETLTLKHGSETVILQKDMPVEVRIVYDKETYLDffILEMLSFKQ (SEQ ID NO 99)>orf00224MELVLPNNYVVIDEEEMMYLDGGAIYIPRWAITGAITGAAYAALAAAGGGGLQLVLASYGLRSALVAGI VKGLGVLGIHIGNAFANTVIRSIASAGIGAGADWIFTNIIDGWDGRRDNQLRIG (SEQ ID NO : 100)>orf00226MKDDQKYLLAGLYSLLVAIFYFPLIESKGIFVSILMAVLLLYLIYFIATVIHIVIIKFIRKKSFKYLVL YPFTYDGSffRFQPINLLYFPEMVRDVIPINLVQEYCQGQPYGLLKKMLKRIRLSREISLLLATIIVYFFTHRILPLS VFTFIFSYILLFAQSYLGGNTVWIGNRRLIIDDEFEKILLSKSYIKEISSARYSEYLTCEYKNLTPIILLAIFENLL DSYLIQNQSKVDLDIFYKVLPLLYKEKYTMGFNYFVSLNYLLYKVGFLGIIYDNEALRDLSKQYLNKNISELQDGSF EDGIQDAVASKQIVVINEFIACLNSRCVPSQYDRFFYKDRPYIFSRKSPIKG (SEQ ID NO 101)>orf00227MKNKRYFFDTILIILLLISTIFCVSPVFIKLDILGTPSHAILTFVLAIPLFYILSQCLHTLLLLVSSI FCKLRPIYFYFIFVIIIGARKYYRILFHQLMGFSPGVAVFYKESQTTKNLFKFYYFLYFTTLISYYFFFTFVYDKP LLLPLIPFSIIIALVQKLYRIENQQLFLLKSKVLTILESKKDCEFNLQDYHEIWKLQSKSELPCVALSYISLIKP YLSESVREQIDLLEVKRFKKINHPISLYGMLDVIKLNLYLRHYNEKNKYESMLKKILEVRPDFVLIEQNIDDSLN SSQPLSLSLAISEIQLLLEVYMGIKHVSIRR (SEQ ID NO : 102)>orf00228MIRKPIIFLLMLPIWGLWIELHLLVSNLQLNLEIPFDFVVSTSLTFFVLILSKIVLDILYALKDLYKK EALITIFPFIFIRRKKVNVRFSPYFSFHRKSLSPDDLRSRIIffSFILEIAIILVFILKIPFAIIMLTTIFFffTIMD INHLVFNKTEFLFNQNKWQKEDSFESDLTKTLKDKIQKSELSYSDLMSLQLYDAMNQSTFLTDSELFEDILKKIE DSHNTLLCTGLVELLLYEMSISNNNNWQEKVDKIRIQLIRINQLDFFYYTSWLRQNFDFCMNREYHKMKSRKLLL SNKKIV(SEQ ID NO 103)>orf00229MELVLPNNYVVIDEEEMMYLDGGAYLSKRACQGICVALAMSPGTFIALTGAAVLTKKLINYIKVGGLGG WLIGAAAGVLAGAAGRIAYCIGYGALNRGCDISGNPYPWDGFISATVR (SEQ ID NO : 104)>orf00230LGWIHIC DSKMSNVDKIRKIHIIVCWVYIFLSFRAIINDTEYFLLIFLAFIYSIVSLPLYSVKNKIVSI CLVINSILLMSFPILINKFFPESFSTYIVLISVFITELIIFHLIGKDFDTKLTNEYKKISQFRSKVSQSPWIKYLEI SSFILTIFPSILYGTVDNHVLTLIFLIKICVDTTIKFLFIRLFDTSTLMKRRIFFLFALDVIAYLFLGYLLVIQKAGYLFSVLLLFSNFSVPFIKAKEYELFKNSK (SEQ ID NO : 105)>orf00232MNKKKMILTSLASVAILGAGFVASSPTFVRAEEAPQVVEKSSLEKKYEEAKAKYDAAKKDYDEAKKKAA EAQKKYEEDQKKTEEKAKKEKEAAKEVDDASLAVQKAHVEYRKVLDSRNSYRNPSDYAKKLAEADKKITEETTKLTN aqtkfqsirttivvpgqselaetkkkaeeakaeekvakrkydyatlkvalakkeveakeleieklqdeistleqeva TAQHQVDNLKKLLAGVDPDDTEAIEAKLKKGEAELNAKQAELAKKQTELEKLLDSLDPEGKTQDELDKEAAEAELNK KVESLQNKVADLEKEISNLEILLGGADSEDDTAALQNKLATKKAELAKKQTELEKLLDSLDPEGKTQDELDKEAAEA ELDKKVESLQNKVADLEKEISNLEILLGGADSEDDTAALQNKLATKKAELEKTQKELDAALNELGPDGDEEETPAPA PQPEQPAPAPKPEQPAPAPKPEQPAPAPKPEQPAKPEKPAEEPTQPEKPATPKTGWKQENGMWYFYNTDGSMATGWL QNNGSWYYLNANGSMATGffVKDGDTWYYLEASGAMKASQffFKVSDKffYYVNSNGAMATGffLQYNGSffYYLNSNGAMA TGWAKVNGSffYYLNANGSMATGffVKDGDTWYYLEASGAMKASQffFKVSDKffYYVNSNGAMATGffLQYNGSffYYLNSN GAMATGWAKVNGSffYYLNANGSMATGffVKDGDTWYYLEASGAMKASQffFKVSDKffYYVNSNGAMATGffLQYNGSffYY LNSNGAMATGWAKVNGSWYYLNANGSMATGffVKDGDTffYYLEASGAMKASQffFKVSDKffYYVNGLGALAVNTTVDGY RVNANGEffV (SEQ ID NO: 106)>orf00233MKIRRRYTHIIRIICILTISFKKQFLSSSLSSLTKRVIMNTAQATFNREAHTTFNRE(SEQ ID NO: 107)>orf00252LKKRMNRWQFLLNQSKEMVGILLLKVKEQELIEFVVNL (SEQ ID NO : 108)>orf00253LIKVIKRKAFGFRNFNNFKKRILMTLNIKKESTNFVLSRL (SEQ ID NO : 109)>orf00257MTYNEKRLTNSLERGHMEQLKNTTDLLGLEDKNIKILSVLKYQTHLVVQAKLDSPAPPCPHCQGKMIK YDFQKASKIPLLDCQGLPTVLHLKKRRFQCKNCLKVVVSQTSIVKKNCQISNMVRQKIAQLLLEKQSMTEIAHRLA VSTSTVIRKLREFKFETDWTKLPKVMSWDEYSFKKSKMSFIAQDFESKSILAILDGRTHAVIRNHFQRYQREVRE LVEVITMDMYSPYYRLAKQLFPKAKIVLDRFHIVQHLSRAMNRVRIQIMNQFDRKSLEYRALKRFWNPRFFVSRL GLNQSTGLIYYTRIASSSVRNDSISPRFECT (SEQ ID NO : 110)>orf00258MGYSLKKSRTYCEQDPEKVNRFLKELNHLSYLTPIYIYETGVETYFYLEYDRALSRQLVSLEEDIII (SEQ ID NO :111)>orf00265LREGCSIYDNLYPSRIVVGDETVEGRKIAELFLSISTHSTANIKNVMLVSPTEAEAIKLFSNTFLALRV AFFNELDFFAERRSLNAEVVIKGVCLDPRIGNFYNNPSFEFGGYCLPKDTKQLKKEFIEINAPVIEAIDISNTNRKQ FIVKQILERKPKIVGIYKLGMKYNSDNYKESAILSIINELLIVGIKILVYEPNLNVSIDNVIFEKNFELFTKQSDLI VANRffDRGLEAYKDKVYTRGIffIRD (SEQ ID NO : 112)>orf00268MLNLQFAETMELTEAELETVYGGEFGNNAVIPAGAWGGLGTSWSITNFWKKYFNHDSSTVNRRHY (SEQ ID NO 113)>orf00272
MKIKEQTRKLAAGCSKHRFEVADRTDEVSSKHCFEVVDRTDEVSNHTYGKVKLTWFEESFEEYK (SEQ ID NO 114)>orf00338LNTSYSFGKKDQFALEHCFCIKLSIFARAVTLFVSCIN (SEQ ID NO : 115)>orf00359MLIGEGYRTFPVLIYTQFISEVGGNSAFAIMAIIIALAIFLIQKHIANRYSFSMNLLHPIEPKKTTKGK MAAIYATVYGIIFISVLPQIYLIYTSFLKTSGMVFVKGYSPNSYKVAFNRMGSAIFNTIRIPLIALVLVVLFTTFIS YLAVRKRNLFTNLIDSLSMVPYIVPGTVLGIAFISSFNTGLFGSGFLMITGTAFILIMSLSVRRLPYTIRSSVASLQ QIAPSIEEAAESLGSSRLNTFAKITTPMMLSGIISGAILSWVTMISKLSTSILLYNVKTRTMTVAIYTEVLRGNYGV AAALSTILTVLTVGSLLLFMKISKSNSITL (SEQ ID NO : 116)>orf00360LIIIASMSTPFVGAYSWILLLGRNEVITKFLTNALYLPAIDIYGFKGIILVFTLQLFPLVFLYVAGTMN SIDNSLLEAAESMGSFGFKPIVTVVLPLLVPTLLAAPCLYL (SEQ ID NO: 117)>orf00362LLSTTEFIGLSIRILSNLHESKILVGLLNQFFFWNLLLHKTKSNVVSDSQMWENSVVLENQPDIAFAGF HIIDFCIIEVKFSIFDTVETCNHTKKGRFPTS (SEQ ID NO : 118)>orf00380VTAPTSITPLLVNTHERKSSQSLTSCLVYVVKTVLTSQHLIYSKLKLK (SEQ ID NO : 119)>orf00382MITIKKQEIVKLEDVLHLYQAVGWTNYTHQPEMLEQALSHSLVIYLALDGDAWGLIRLV⑶GFSSVLV QDLIVLPIYQRQGIGSALMKEALEDYKDAYQVQLVTEQTERTLGFYRSMGFEILSTYNCIGMTWMNRKK (SEQ ID NO 120)>orf00441MGAFVLFLFQLTINRYKKKSFYffYKEVIESNGETLDN (SEQ ID NO : 121)>orf00465VAIDKIAGITSEKDSRAHQIFRISPTCSRCFCNDELVKWVARTIFLQFTKRCCLRSGNITRSNSVTLDI GSTVFRRNVAGQHFQAPFSSSISANCFTSQFAHHRTNIDNLSMPFLYHRRNNCL (SEQ ID NO: 122)>orf00466LFDLLDHGLDTVLVCHVTDISMGFDANFTISFNPFIDQILIDIVKDNSSAGFSVGFGNSKSNSIRSAGD ESNFSF (SEQID NO 123)>orf00478MKSLARLLNIHVFISIFLFFALISGAVSHTVLLLLLLFLPALNKGLEKIQSKRIPVLNAALFFLLISFPQLLTNPVQWKFSIFLVVTIISSLAYFYNFYQVVKEVDQKQLI (SEQ ID NO : 124)>orf00480LEAAGEIETEFQGWIVLVVFNHIDSLSRDTDILGEFELGNTQFLAKFFHTIHLVSFLIYVVYI (SEQ ID NO 125)>orf00485MVDRTDEVSSKHGFEVVDKEKLMWFEEVFEECKKILVS (SEQ ID NO : 126)>orf00492
MEGVNHVDIIKVSCGSFISQVNWMMKGKIPNREGFKFSVARLDAIDLVVVHIGHTRCQFSRTGSRSGYD NQVATDFDVVVFAHAFWGNDVIHIRRISFDWIMKIRINSVFLKLVAEGICSGLTSVLCNDNGTNKNP (SEQ ID NO 127)>orf00493 MFNVASINGNHNLNLLFQFLQELDFVVRFITRKDTSSVEIF (SEQ ID NO : 128)>orf00495LFFHFLPLDSIIIKNWKLGNYGAKKEIKKIKQTLAQNFKKCYHIL (SEQ ID NO : 129)>orf00498MQLTSVTAPTGTDNENIQKLLADIKSEYRFDGRPEFVLLGCLQESDCR (SEQ ID NO : 130)>orf00501MIDIHSHIVFDVDDGPKSIEDSKALLREAYNQGVRMIVSTSHRRKGMFETPEEKIVTNFIKVREIAKEV ADDLVIAYGAEIYYTLDALEKLEKKKFLPLMIVVML (SEQ ID NO: 131)>orf00502MHTSYREIHTRLSNILMLGITPVIAHIERYDALENNEKRVRELIDMGCYTQIDSYHVSKPKFFGEKYKF MKKRARYFLERDLVHVVASDMHNLDSRPPYMQQAYDIIAKKYRAKKAKELFVDNPRKIIMDQLI (SEQ ID NO: 132)>orf00503MKEQNTLEIDVLQLFRALWKRKLVILLVAIITSSVAFAYSTFVIKPEFTSTTRIYVVNRNQGEKSGLTN QDLQAGSYLVKDYREIILSQDVLEEVISDLKLDLTPKGLANKIKVTVPVDTRIVSVSVNDRVPEEASRIANSLREVA AQKIISITRVSDVATLEEARPAISPSSPNIKRNTLIGFLAGGIGTSVIVLLLELLDTHVKRPEDIEDTLQMTLLGVV PNLGKLK (SEQ ID NO : 133)>orf00505MAKGHHIKLKVKDKIANVLTCNTISINSITSHSNSTQFMPFGMVLTQPLNIRRHPVFSNFNLSSFYILT ERTIQ (SEQ ID NO : 134)>orf00506MKIAIAGSGYVGLSLAVLLAQHHEVKVIDVIKDKVESINNRKSPIKDEAIEKYLVEKELNLEASLDPAH VYKDVEYAIIATPTNYDVDLNQFDTSSVEAAIKTCMEYNDTCTIVIKSTIPEGYTKEVREKFNTDRIIFSPEFLRES KALYDNLYPSRIVVGTDLDDSELTKRAWQFADLLKGGAIKEEVPILVVAFNEAEVAKLFSNTYLATRVAYFNEIDTY SEVKGLNPKTIIDIVCYDPRIGSYYNNPSFGYGGYCLPKDTKQLKASFRDVPENLITAVVQSNKTRKDYIAGAILAK QPSVVGIYRLIMKSDSDNFRSSAVKGVMERLDNYGKEIVIYEPTIECDTFMGYRVIKSLDEFKNISDIVVANRMHDD LRDIQEKLYTRDLFGRE (SEQ ID NO : 135)>orf00507MYTFILMLLDFFQNHDFHFFMLFFVFILIRffAVIYFHAVRYKSYSCSVSDEKLFSSVIIPVVDEPLNLF ESVLNRISRHKPSEIIWINGPKNERLVKLCHDFNEKLEN匪TPIQCYYTPVPGKRNAIRVGLEHVDSQSDITVLVD SDTVWTPRTLSELLKPFVCDKKIGGVTTRQKILDPERNLVTMFANLLEEIRAEGTMKAMSVTGKVGCLPGRTIAFRT EILRECIHEFMNETFMGFHKEVSDDRSLTNLTLKKGYKTVMQDTSVVYTDAPTSWKKFIRQQLRWAEGSQYNNLKMT PWMIRNAPLMFFIYFTDMILPMLLISFGVNIFLLKILNITTIVYTASWWEIILYVLLGMIFSFGGRNFKAMSRMKWY YVFLIPVFIIVLSIIMCPIRLLGLMRCSDDLGffGTRNLTE (SEQ ID NO : 136)>orf00508
LIFEKEKCFLMLRKNLKYQIMTRAGTILAILFFIILGIIVEVLF (SEQ ID NO : 137)
>orf00509MKKVKKAVIPAAGLGTRFLPATKALAKEMLPIVDRPTIHFVIEEALRSGIEDILVVTGKSKRSIEDYF DSTFELEYSLRKQGKMELLKSVNESTDIKVHFVRQSSPRGLGDAVLQAKSFV⑶DPFVVML⑶DLMDITDSTAVPL TRQLMDDYNATQASTIAVMPVRYEDVSSYGVISPRLESSNGLYSVDAFVEKPKPEEAPSNLAIIGRYLLTPEIFS ILETQKPGAGNEIQLTDAIDTLNKTQSVFAREFVGKRYDV⑶KFNFMKTSIDYALQHPQIKESLKNYVIALGKQL EKLDDCSSSGHL (SEQ ID NO: 138)>orf00510MNCIESYQKWLNVPDLPAYLKDELLSMDDKTKEDAFYTNLEFGTAGMRGYIGAGTNRINIYVVRQATEG LAKLVESKGETAKKAGVAIAYDSRHFSPEFAFESAQVLAAHGIKSYVFESLRPTPELSFAVRHLGAFAGIMVTASHN PAPFNGYKVYGSDGGQMLPADADALTDYIRAIDNPFAVALADLEEAKSTGLIEVIGETLDSAYLEEVKSVNINQDLI DQYGRDMKIVYTPLHGTGEMLARRALAQAGFESVQVVEAQAKPAPDFSTVASPNPESQAAFALAEELGRQVDADVLV ATDPDADRLGVEIRQADGSYWNLSGNQIGALIAKYILEAHKQAGTLPKNAALAKSIVSTELVTKIAESYGATMFNVL TGFKFIAEKIQEFEEKHNHTYMFGFEEG (SEQ ID NO: 139)>orf00520MNKGLFEKRCKYSIRKFSLGVASVMIGAAFFGTSPVLADSVQSGSTANLPADLATALATAKENDGRDFE APKVGEDQGSPEVTDGPKTEEELLALEKEKPAEEKPKEDKPAAAKPETPKTVTPEWQTVEKKEQQGTVTIREEKGVR YNQLSSTAQNDNAGKPALFEKKGLTVDANGNATVDLTFKEDSEKGKSRFGVFLKFKDTNNNVFVGYDKDGWFWEYKS PTTSTWYRGSRVAAPETGSTNRLSITLKSDGQLNASNNDVNLFDTVTLPAAVNDHLKNEKKILLKAGSYDDERTVVS VKTDNQERVKTEDTPAQKETGPVVDDSKVTYDTIQSKVLKAVIDQAFPRVKEYTLNGHTLPGQVQQFNQVFINNHRI TPEVTYKKINETTAEYLMKLRDDAHLINAEMTVRLQVVDNQLHFDVTKIVNHNQVTPGQKIDDERKLLSSISFLGNA LVSVSSDQTGAKFDGATMSNNTHVSGDDHIDVTNPMKDLAKGYMYGFVSTDKLAAGVWSNSQNSYGGGSNDWTRLTA YKETVGNANYVGIHSSEffQffEKAYKGIVFPEYTKELPSAKVVITEDANADKKVDWQDGAIAYRSIMNNPQGWEKVKD ITAYRIAMNFGSQAQNPFLMTLDGIKKINLHTDGLGQGVLLKGYGSEGHDSGHLNYADIGKRIGGVEDFKTLIEKAK KYGAHLGIHVNASETYPESKYFNEKILRKNPDGSYSYGWNWLDQGINIDAAYDLAHGRLARWEDLKKKLGDGLDFIY VDVWGNGQS⑶NGAWATHVLAKEINKQGWRFAIEWGHGGEYDSTFHHWAADLTYGGYTNKGINSAITRFIRNHQKDA WV⑶YRSYGGAANYPLLGGYSMKDFEGWQGRSDYNGYVTNLFAHDVMTKYFQHFTVSKWENGTPVTMTDNGSTYKWT PEMRVELVDADNNKVVVTRKSNDVNSPQYRERTVTLNGRVIQDGSAYLTPWNWDANGKKLSTEKEKMYYFNTQAGAT TWTLPSDWAKSKVYLYKLTDQGKTEEQELTVKDGKITLDLLANQPYVLYRSKQTNPEMSWSEGMHIYDQGFNSGTLK HWTISGDASKAEIVKSQGANDMLRIQGNKEKVSLTQKLTGLKPNTKYAVYVGVDNRSNAKASITVNTGEKEVTTYTN KSLALNYVKAYAHNTRRDNATVNDTSYFQNMYAFFTTGSDVSNVTLTLSREA⑶QATYFDEIRTFENNSSMYGDKHD TGKGTFKQDFENVAQGIFPFVVGGVEGVEDNRTHLSEKHYPYTQRGWNGKKVDDVIEGNWSLKTNGLVSRRNLVYQT IPQNFRFEAGKTYRVTFEYEVGSDNTYAFVVGKGEFQSGRRGTQASNLEMHELPNTWTDSKKAKKATFLVTGAETGD TWVGIYSTGNASNTRGDSGGNANFRGYNDFMMDNLQIEEITLTGKILTENALKNYLPTVAMTNYTKESMDALKEAVF NLSQADDDISVEEARAEIAKIEALKNALVQKKTSLVADDFASLTAPAQAQEGLANAFDGNLSSLWHTSWGGGDVGKP ATMVLKEPTEITGLRYVPRGSGSNGNLRDVKLVVTDESGKEHTFTTTDWPDNNKSKDIDFGKTIKAKKIVLTGTKTY GDG⑶KYQSAAELIFTRPQVAETPLDLSGYEAALAKAQKLTDKDNQEEVASVQASMKYATDNHLLTERMVEYFADYL NQLKDSATKPDAPTVEKPEFKLSSLASDQGKTPDYKQEIDRPETPEQILPATGESQSDTALFLAGVSLALSALFVVK TKKD (SEQ ID NO : 140)
>orf00523LQIAQESSQDTDGINPPVVEEAMVFDRNDCLNQICGNIISLGIDAAFRTQVSNELIFIVVDFTRSCCN (SEQ ID NO 141)>orf00525MLNLMWMKIFHRNRTFLFCFLDFKVDVISIINARIVRR (SEQ ID NO : 142)>orf00526MYNSQALRQIVVVGSIDHLFKRHSSICEIFGLRKRCLSFLff (SEQ ID NO : 143)>orf00537MKLLKKTMQAGLTVIFFGLLATNTVFADNSEGWQFVQENGRTYYKK⑶LKETYWRVIDGKYYYFDSLS GEMVVGWQYIPFPSKGSTIGPYPNGMRLEGFPNSEWYYFDKNGVLQEFVGWKTLEIKTKDSVGRKYGEKREDSEDK EEKRYYTNYYFNQNHSLETGffLYDQSNffYYLAKTEINGENYLGGERRAGffINDDLTffYYLDPTTGIMQTGffQYLGN KWYYLRSSGAMATGWYQEGTTWYYLDQPNGDMKTGWQNLGNKWYYLRSSGAMATGWYQEGTTWYYLDQPN⑶MKTGW QNLGNKWYYLRSSGAMATGWYQDGSTffYYLNAGNGDMKTGffFQVNGNffYYAYSSGALAVNTTVDGYSVNYNGEffVR (SEQ ID NO 144)>orf00541MTTGWFQVNGRWYYAYSSGALAVNTTVDGYFVNYNGEWVQ (SEQ ID NO : 145)>orf00551MSLADLLEELEAAKDSKKARSMEAYMRHQFSFLGIAVPERNKLYKNIFQKRKKQRLSIGILQTLAGKRI LENTNMWLLTI (SEQ ID NO : 146)>orf00552MEKILLHNLNQTEFFINKAIGWTLRDYSKTNPTWVTCFIEKNKERMAELSIKEASKYL(SEQ ID NO: 147)>orf00555VLEILKEYLLLEE⑶YIFTNNGSPLMITCFNYFLKNSFRKSEIKKDDFVLTAHVFRYSHISLLAELEVP ITAIMDRVDYTNETKILSVYTHVTEKMKSNITEKLDKLVLEND(SEQ ID NO: 148)>orf00580LVIFKNCSHCTSNCKSRTVQGMKEFHLAICFITVTDLSTTGLEIFXXXFHSLIN (SEQ ID NO 149)>orf00581MNXXARGFSFVCKDFEVAAHFASSDIGSNLIDMAPRNLDKLFDIDIWVKFQSLISDKEFPNFPSDREVG SACRTEEYCFVK (SEQ ID NO : 150)>orf00587LQKPLFQILQKLVKISQAFIHDSNFFLAHAINNFXXHSFIN (SEQ ID NO : 151)>orf00590VGFSLLLLLIFCLFCLLFNVSNQVTNCFQVIFCFDLDIKSIFDF (SEQ ID NO : 152)>orf00614 VNIDSSEFYISHITDGIFDSFLDSNRYLRNFYSVLKVEIDICCEFFVHVFKINATAE (SEQ ID NO: 153)>orf00615
VNTLYLCSSNSNDFFKYTffGDNDFAKLFFNSHRMTSF (SEQ ID NO 154)>orf00625
LFSPRPGiiDNGKGTTFLNFFLNIHKFSFFDSLFFLFQ (SEQ ID NO : 155)>orf00627VKEEKKAIVLGADNAYMDKVETTLKSLCVHHYNLKFYVFNDDLPREWFQLMEKRLETLNSEIVNV (SEQ ID NO 156)>orf00643LAQISILHFDFLSIDKHSHTVFNTLRKSLQTTLALSATSKQCFEQLAASFLVCSLIFIEYKV (SEQ ID NO 157)>orf00652MSLITHRRFISSKVTRQKFVDNQIDLKYYIWRYSHALCGIDVAKNKHDVTALNVSGKTVLKPLTFSNNK AGFELLDLSLRQLNQDYLIALEDTGHYAFNLLNFLHEQGYKVYTYNPLLIKKFAKSLLLRKTKTDKKDAHGIALKLL SDPNREQFQHDNRQVELKILARHIHRLKKKQSDWKVQYTRCLDIIFPELDKIVGKHSEYTYQLLTCYPNPQKRLEAG FDKLIEIKRLTASKIQDILSVAPRSIGTTSPAREFEIIENIKHYKRLIDKAETCVNDLMAEFNSVITTVTGIGNRLG AVILAEIQNIHAFDNPAQLQAFAGLDSSIYQSGQIDLAGRMVKRGSPHLR (SEQ ID NO: 158)>orf00654MDTKSSCLITTGRNDSPSTCLPRVASNNDRFSSEFRIIPDFHCSKKGIHVNMDDFS (SEQ ID NO 159)>orf00657MDKMKPVFQALNKELIQENLTLTIICVGGYVLEYHGLRATQDVDAFYDQNQKINEIIARVGKQFNLNTH EELWLNNHVANMNKQPPLSLCESLYSFENLTVLVVPIEYVLGMKMMSIREQDLKDIGAIIKYKNFHSPFDTFKYLKD MGFDTIDLSVLLEGFSYAYGMDffLEKFFKENQDKLREFY (SEQ ID NO : 160)>orf00663MIPLYRTDNDITKFFTKIRNGHLAKTAGGLDDKFHEANASTSKAFDRQGVGEVNDIRDSAGSQELRIND KRKTENILFLEIRVRIFRVPHPNDSFFSSHFLG (SEQ ID NO : 161)>orf00664VLSQGDKDITILDAGLLKNGKIGPVTKDTNDIKATD匪IENSFVLLNQQNIMLFCNQGATEGKTNFSPS DKDNFHNKTYFFMM (SEQ ID NO: 162)>orf00669MKIKEQTRKLAAGCSKQCFEIVDRTDEVSSKHGFEVVDETDEVSSKHGFEIVDETDEVSNHTYGKAKLT WFEEIFEEYKMMGKAGQLVFFDVYRLVRQVS (SEQ ID NO: 163)>orf00698MEKFNFKNNIGQENKLLQIEIYKFTNFCKLQNYTSVNIFSKDIFEAIVN (SEQ ID NO : 164)>orf00701VRIKSIYWNFGQNKPEKSFRYIDTSSIDRKKNIINYKNLQYLSPEQAPSRARKLVSQNSVLFSTVRPYL KNIAVVRELKEYLIASTAFIVLDTLLNETYLKYYLLSDNFINRVNNKSTGTSYPAINDYNFNLLLIPLPPLSEQQRI VEAIESALEKVDEYAESYNRLEQLDKEFPDKLKKSILQYAMQGKLVEQDPNDESVEVLLEKIRAEKQKLFEEGKIKK KDLDISIVSQ⑶DNSYYGNIPMNWWIKIKDIFSINTGLSYKKGDLSINKGVRIIRGGNIKPLEFSLLDNDYYIDTQ FISSEQVYLKHNQLITPVSTSLEHIGKFARIDKDYDGVVAGGFIFQLTPFESSEIISKFLLFNLSSPLFYKQLKAITKLSGQALYNIPKTTLSELLIPLAPFEEQELITQKVEKLFEKVNQLWK(SEQ ID NO : 165)>orf00720MIRKVNHNIFKHRSVVIFTLTNSYFCKFFINDISISFHSHQHFCWIIIQIK (SEQ ID NO : 1 66)>orf00724LDNIHIVLDSLNAVSGIQDFICDGLAIFCNQITSGCSSCK (SEQ ID NO : 167)>orf00735MNIAWILLYALVINGLEIVIFFKVDGIGLTFDRIFKAFLLKFLLGIIFTTFQFLAVSKYLSYFIEPLFG IGLSFLLLRGLPKKILIFYGLFPMILVELFYRGVSYFVLPFLGQGIVDGDGNPIFLLIMIFVCFIVLVFLKWLDYDF TRLRREFLDTGFQKSLTKINWAMGAYYLVMQSLSYLEYEQGIQSTTVRHLILVFYLLFFMGGIKKLDTYLKEKLQEE LNQEQTLRYRDMERYSRHIEELYKEIRSFRHDYTNLLTSLRLGIEEEDMEQIKEIYDSVLRDSSQKLQDNKYDLGRL VNIRDRALKSLLAGKFIKAREKNIVFNVEVPEEIQVEGMSLLDFLTIVSILCDNAIEASAEASQPHVSIAFLKNGAQ ETFIIENSIKEEGIDISEIFSFGASSKGEERGVGLYTVMKIVESHPNTNLNTTCQNQVFRQVLTVIHAE (SEQ ID NO 168)>orf00737MISQEDILKACEVAEIRQDIERMPMGYQTQLSDGAGLSGGQKQRIALARALLTKSPVLILDEATSGLDV LTEKKVIDNLMSLTDKTILFVAHRLSIAERTNRVIVLDQGKIIEVGIHQELMQAQGFYHHLFNK (SEQ ID NO 169)>orf00738MSSKISIGQLITFNTLLSYFTTPMENIINLQTKLQSAKVANNRLNEVYLVESEFQVQENPVHSHFLMGD IEFDDLSYKYGFGRDTLTDINLTIKQGDKVSLVGVSGSGKTTLAKMIVNFFEPYKGHISINHQDIKNIDKKSLAPSY (SEQ ID NO 170)>orf00740MKSTLGIISVGLVITYILQQVMSFSRDYLLTVLSQRLSIDVILSYIRHIFELPMSFFATRRTGEIISRF TDANSIIDALASTILSLFLDVSILILVEGVLLAQNPNLFLLSLISIPIYMFIIFSFMKPFEKMNHDVMQSNSMVSSA IIEDINGIETIKSLTSEENRYQNIDSEFVDYLEKSFKLSKYSILQTSLKQGNKISSEYPYPMVWRSISHVE (SEQ ID NO 171)>orf00742MTSYKRTFVPQIDARDCGVAALASIAKFYGSDFSLAHLRELAKTNKEGTTALGIVKAADEMGFETRPVQ ADKTLFDMSDVPYPFIVHVNKEGKLQHYYWYQTKKDYLII⑶PDPSVKITKMSKERFFYEWTGVAIFLATKPSYQP HKDKKNGLLSKLPSSDFQTKISHCLHCSLKLIGHYYQYRWFLLSPRNLG (SEQ ID NO : 172)>orf00767MGLIKTLAKIYGNYFLTVQGVKVMKTIKKDDHVVVGLGKLFIADKLMDTARffLIKPEDKK(SEQ ID NO 173)>orf00768MKFFffGLLAIIFIKPIIGIVKFFWMIISFAVQLLFYKIVFKILDffLFKLI (SEQ ID NO : 174)>orf00776MHSQTFQFLLMTDKTSLLHRKHRSFIRNIHSKFLILFDLLCGILSRNDSNHNPIS (SEQ ID NO: 175)>orf00779
MARTELPDKIETERLVLRVRTVADAEDIFDYASLPEIAYPAGFPPVKTLEDEIYYLEHILPERNQKENL PAGYGIVVKGTDKIVGSVDFNHRHEDDVLEIGYTLHPDYWGRGYVPEAARALIDLAFKDLGLHKIELTCFGYNLQSK RVAEKLGFTLETRIRDRKDVQGNRCDSLIYGLLKSEWEE (SEQ ID NO : 176)>orf00781 MSDVKEEVSSLSEKQLRQIDVEYAELNDSDIIERLAYLEINNNEKRIVISDIEPTKEIMSVSDQIFEI QKNFQKIK匪FELFISDVSDFLSIKNKLESKELEIEEADVNRFMIHLLSSGKLFVDFNENQIKQKYSKDSEEFDCI HGFASYQYDINFTYRFCHSLRNYSQHTDLPINEVKAVSPDDETVIIDFYIDLDYLLNSNFKffKKLKGELIKLNQE TSKIDAIALVKEYFNALTELYGNYNKLFLKLNHNTLVDIKSKLESLKLKHSRYYISKISKYDLKYNPGNYTMSPL AAFAEIEEIYIELSKIGLVKIVNKSN (SEQ ID NO: 177)>orf00785MSKHPHYELLNLIGYGLAKFDKLFIKEFQCSSKSEFYRYVVSLGIAETTGVVKNRMDLFDPYFDNNRKG WWQKAEVYRFRKDLIDMMFGNEDVHSYAEIVKMLLASEGKKTGITIVEKPIVRTKFKRLQETGMEAENYFILHFDKE EKFQGGQLTDARLYGDGYDFQVDVQEYSYLAEVKGIRKSKGRVRLTAKEFEKVKEFQSDFILSLVTNLDDIPKLVLI DNPLKHFEFKKNIIKNEIIEYRSVEDLY (SEQ ID NO: 178)>orf00787LSTCWNGKFCHICVALFHCFRAFKLALNEILCLLTNVSFIFVSVAF (SEQ ID NO : 179)>orf00788LLRKQEREYLRAENAILKKLRELRLKEEKEKEERQKLFKN (SEQ ID NO : 180)>orf00809LKHLFCHFNPLWIDEIIRLAYKDQDTKDVKSKVKIGN (SEQ ID NO : 181)>orf00856MKEIAFDAFYQLYQNDQLSLVDVREVDEFAALHLEGAHNLPLSQLADSYD (SEQ ID NO : 182)>orf00859MVSNHKIACFQLFDKVGIFSLLDELNSLANKAHINLLNCF (SEQ ID NO : 183)>orf00871MDFFFMNEVKEQVLFRDNHSEHIFWIEGVSDFMIKVNTALW (SEQ ID NO : 184)>orf00878MKIKEQTRKLAAGCSKHCFEVVDRTDEVSNHTHGKATLTWFEEIF (SEQ ID NO : 185)>orf00885MKIKEQTRKLAAGCSKHSFEVVDKTDEVSSKHGFEVVDETDEVSSKHGFEVVDETDEVSNHIYGKATLT KFELDFRRV (SEQ ID NO : 186)>orf00890MEELVTLDCLFIDGTKIEANANKYSFVWKKTTEKFSAKLQEQIQVYFQEEITPLLIKYAMFDKKQKRG YKQSAKNLANWHYNDKEDSYIHPDGWCYRFHHIKYQKTQTDFQQEIKVYYADEPESAPQKGLYMNERYQNLKAKEC QALLSPQDRQIFAQRKIDVEPVFGQIKACLGYKRCNLRGKRQVRIDMGLVLMANNLLKHSEMK (SEQ ID NO 187)>orf00892MHIHYNTNQTTLPLEISSFLPQDHLVFTIEKVVNTLEDCHFHAFYHAFDRPSYHLKMLVSTLLFAYSQG IFSGRKIEKffKS (SEQ ID NO : 188)
>orf00894LRLWVIFVMKVMKSYNTLNDYYRKLFGEKTFKVPIDAGFDCPNRDGTVAHGGSTFCTVSGS ⑶ AIVAP DAPIREQFYKEIDFMHRKWPDVQKYLVYFQNFTNTHEKVEVIRERYEQAINEPGVVGINIGTRPDCLPDETIEYLAE LSECMHVTVELGLQTTYEATSDLINRVHSYEL(SEQ ID NO 767)>orf00896 VETVKRLRKYPKIEIVSHLINGLPGETHEMMVENVRRCVTDNDIQGIKLHLLHLMTNTRMQRDYHEGR LQLMSQDEYVRVICDQLEIIPKHIVIHRITCDAPRDMLIGPMffSLKKffEVLNSIEMEMRRRGSVQGCKAVKQEFEN EKTT (SEQ ID NO 189)>orf00908VQVCVFTNFCFFHCFSSLANCRLFNLRGICLPCISYQ (SEQ ID NO : 190)>orf00915VFKKDRFSIRKIKGVVGSVFLGSLLMAPSVVDAATYHYVNKEIISQEAKDLIQTGKPDRNEVVYGLVYQ KDQLPQTGTEASVLTAFGLLTVGSLLLIYKRKKIASVFLVGAMGLVVLPSAGAVDPVATLALASREGVVEMDGYRYV GYLS⑶ILKTLGLDTVLEETSAKPGEVTWEVETPQSTTNQEQARTENQVVETEEAPKEEAPKTEESPKEEPKSEVK PTDDTLPKVEEGKEDSAEPSPVEEVGGEVESKPEEKVAVKPESQPSDKPAEESKVEPPVEQAKVPEQPVQPTQAEQP STPKESSQQENPKEDRGAEETPKQEDEQPAEAPEIKVEEPVESKEETVNQPVEQPKVETPAVEKQTEPTEEPKVEVT SIPQTTRYEEDLTKEHGTREVVKEGKNGSRTVTTPYILNATDGTTTEGTSTTDEAEMEKEVVRVGTKPKEKLAPVLS LTSVTDNAMLRSARLTYHLENTDSVDVKKIHAEIKNGDKVVKTIDLSKERLSDAVDGLELYKDYKIVTSMTYDRGNG EETSTLEETPLRLDLKKVELKNIGSTNLVKVNEDGTEVASDFLTSKPVDVQNYYLKVTSRDNKVFRLTVEKIEEVTE EGQPLYKVTAKAPNLIQHTDATKMQDEYVYYIEKTRATDGDIYYNFNDLVNAMNKNKTGTFKLGADLNATGVPTPAK SYVTGDFRGTLTSVDGEHYTIHNTSRPLFNNIIGGTIKDINLGNVNIHMPWANNVASLANIIKGGTTIENVKVTGNV LGKDWVSGFIDKIDSGGTLRNVAFIGNVTSVGTGGSFLTGIVGENWKGLVEQAYVDANIRGKKAKAAGIAYWSQNGG DNYAVGRYGAIKKSVVKGSIDVEKPIEVGGAVGSLNYLGYIEDTVAMMKVKNGEIFYGSHDIDTDPYYTGERVNRNF IVDGVSEGKSSYKYSKQQNRIKSVSQEEADKKIKELAITADKYAITEPIVNKLNALTTRDNEYRTTQDYKADRELAY RNIEKLQPFYNKEWIVDQGNKVPSNSKLLTTEVLSVTGMKDGQFVTDLSEIDKIMIHYADGTKEEMNVTAVADSKVK QVREYDVTDLGVVYTP匪VDKNRDQLIADVKAKLSSVELISPEVRALMDKRGKAEENTEGRQNGYIRDLFLEESFAE VKAGLGKLVKALVENEDYQLNSDEAAMRALIKKVEDNKAKIMMGLAYLNQYYSFKYAELSIKDIMMFKPDFYGKNVN VLDFLIKIGSSERNVK⑶RTLEAYRETIGGTIGINELNGFLHY匪KLFTNHIDINDWFKKAIEKNAYWEQPSTNPA FANKKYRLYEGINNGQHGRMILPLLNLKNAHLFMISTYNTISFSSFEKYGKDTDEKREKFKSEINKRAKEQVNYLDF WSRLATDNVRDKLLKSQNVVPTPVWDNHNSPNGWASRHGHIDGKPDYAPIREFFGRINKYHGYKYGYGAYAYIFAAP QPMDAVYFVMTDLISDFGTSAFTHETTHINDRMAYYGGHWHREGTDLEAFAQGMLQTPSVSNPNGEYGALGLNMAYE RQNDGNQWYNPNPNKLKSRAEIDHYMKNYNEALMMLDYLEAESVLPKLKGNNDRWFKKMDKQMRKDGQPHQFDKIRD LNNEEKKIQLASIEDLVDNNFMTKHGAPGNGTYNPSDFSSAYVNMNMMTGVYGGNSSDGAPGAASFKHNTFRMWGYF GYENGFIGYASNKYKAEANKAGQTLSDKYIINKVSGGTFNTLEAWKKEWFKQIKTKAQKGFTAIEIDGKTIDSYEKL KDLFDKAVEEDLKGTGTDKTVKLKEKVYKQLLKNTDGFSGDLFTAPQA (SEQ ID NO: 191)>orf00933V⑶RIFIAFLQKLGLLDNLTGIREKLHPITGQGDSLGIADKDLNAHFIFQISHCIGETWLSDKELLGCL IHGASFDDFDNIM (SEQ ID NO: 192)>orf00941
VSRWDGHSDKGEAPAGKTSYAWIWTKWGEQVAFYCDYD (SEQ ID NO 193)>orf00955MKLFKPLLTVLALAFALIFITACSSGGNAGPSSGKTTAKARTIDENKKSGELRIAVF⑶KKPFGYVDND gsyqgydielgnqlaqdlgvkvkyisvdaanraeylisnkvditlanftvtderkkqvdfalpymkvslgvvspktg LITDVKQLEGKTLIVTKGTTAETYFEKNHPEIKLQKYDQYSDSYQALLDGRGDAFSTDNTEVLAWALENKGFEVGIT SL⑶PDTIAAAVQKGNQELLDFINKDIEKLGKENFFHKAYEKTLHPTY⑶AAKADDLVVEGGKVD (SEQ ID NO 194)>orf00988MDTPDENGYVADDYRITYLEAHIKAMRDAIYQDGVDLLGYTTWGCIDPVSAGTGEMNKRYGFIYVDRDN vgngalkrskkksfywykdvidsngasig (seq id no: 195)>orf01015MTEPDFWNDNIAAQKTSQELNELKNTYNTFHKMEELQDEVEILLDFLAEDESVHDELVAQLAELDKIM TSYEMTLLLSEPYDHNNAILEIHPGSGGTEAQDW⑶MLLRMYTRYGNAKGFKVEVLDYQA⑶EAGIKSVTLSFEGP NAYGLLKSEMGVHRLVRISPFDSAKRRHTSFTSVEVMPELDDTIEVEIREDDIKMDTFRSGGAGGQNVNKVSTGV RLTHIPTGIVVQSTVDRTQYGNRDRAMKMLQAKLYQMEQEKKAAEVDSLKGEKKEITWGSQIRSYVFTPYTMVKD HRTSFEVAQVDKVMD⑶LDGFIDAYLKWRIS (SEQ ID NO: 196)>orf01045MQVIKRNGEIAEFNPDKIYQAILKAAQTVYVLTDDLRQNLAQVTKKVVLDLQEAKVERATISMIQSMVE HRLLGAGYITIAEHYISYRLQRDLERSGY⑶HIAVHLHFEQIR (SEQ ID NO: 197)>orf01068MELFKTWKKNMVLYGLKSQIGTVYRNNDRTTSFYDVGNFLYLAGELDSRFWEDFVRKYGLDYKIIISEN TNWQDFLHRKVGLNSFTRYSFKDKANFQVEFLNNLVTHLEEGYNIVPIDNHIYNCFSTEEWSQDLQ⑶FESYQDFVL KGGFGFVILKNNELIAGISSGLVYRKAVEVEVATRPNEQGNGFAKKLGAAMILESLNRDMFPLffDAHNEASKKVAEFLGYELSEPYEAFELEEILI (SEQ ID NO : 198)>orf01090LGSDRKALHKPVYLFffCESFDILFCTffSSQFSVLKAFI (SEQ ID NO : 199)>orf01110MKVINQTLLEKVIIERSRSSHK⑶YGRLLLLGGTYPYGGAIIMAALAAVKSGAGLVTVGTDRENIPALH SHLPEPMAFSLQDQQLLKEQLEKAEVILLGPGLRDDASGENLVKQVFVNLSQNQILIVDGGALTILARTSLSFPSSQ LILTPHQKEffEKLSGITIEKQKEDATASVLTSFPQGTILVEKGPATRIWEVGQSDYYQLQVGGPYQATGGMGDTLAG MIAGFVGQFRQASLYERVAVATHLHSAIAQELSQENYVVLPTEISRYLPKIMKIICQQDRVSKDKLV (SEQ ID NO 200)>orf01114VLASNRKFIFFFFRIGILILKNIKSFNQFLALFHKIPSHDGSRKSLSWSDGKSLKXXFIH(SEQ ID NO 201)>orf01121VLDSKEELKESENDAPKLETPLREEPRLAPQTLLEASEVLENKREESKVGITEPAQDSPILAPVEETKE EAVTEKPTNTRSLTAEDLVKISKGELHLENDLIDESFYGEKALDLE⑶DYQDGIKNKDGKDYLGYNSHPLLADSDGD GLADGEDDNKKEWYVTDRDSLLFMELAYRDDDYIEKILDHKNLFPSLYLDRQEHKLMHNELAPFWKMKKAYYTDSGLDAFLFETKSDLPYLKDGTVHMLAIRGTRVNDAKDLSADFVLLGGNKLAQADDIRKVVGELAKDISITKLYMTGHSLG GYLAQIAAVEDYQKYPDFYNHVLRKVTTFSAPKVITSRTVWDAKNGF (SEQ ID NO 202)>orf01148MGRNPKTRPEERTELERLQSENEYLRAENAILKKLRELRLKEEKEKEERQKLFKN (SEQ ID NO 203)>orf01150LSTCWNGKFCHICVALFHCFRAFKLALNEILCLLTNVSFIFVSVAF (SEQ ID NO 204)>orf01165
VVLSTSAILVACGKTDKEADAPTTFSYVYAVDPASLGYSIATRTSRTDVIGNVIDGLMENDKYGNVAPS QKDYDLNSTGWAPSYQDPASYLNIMDPKSGSAMKHLGITKGKDKDVVAKPGLDKYKKLLEDAVSETTDLEKRYEKYA KAQAWSTDSSLLMPTASSGGSPVVSNVVPFSKPYSQVGIKGEPYIFKGMKLQKDIVTTKEYNEVFKKWQKEKLESNS KYQKELEKYIK (SEQ ID NO 205)>orf01169LNFDFFIFLAHFIPLFTFSILQENPKTSKKKLYIRLL (SEQ ID NO 206)>orf01176MGFSMKLIHDLDTHTTHSTAKMLYNVKAIKNDFSIRE (SEQ ID NO 207)>orf01191LIRIIRNIYRSGEGNTSVFQSFIDQINSNQFCYGSNFDRLRCILLIENFTSICLNSNRMFSGNGKILSN SSRSTP (SEQ ID NO 208)>orf01202MIYFDNSATTKPYPEALETYMQVASKILGNPSSLHRL⑶QATRILDASRHQIADLIGKKTDEIFLTSGG TEGDNRVLQGVAFEKAQFGKHIIVSPLPHSAVLE (SEQ ID NO :209)>orf01223MKIKEQTRKLAAGCSKHCFEVVDKTDEVSSKHGFEVVDETDEVSNHTYGKATLTRIEEIFEEYKSS (SEQ ID NO 210)>orf01233LVYAPFSFNILLDYITFDFKILLFSVFLAINRFHNDFIQFLL (SEQ ID NO 211)>orf01236MSGYSGLSFFEVALAEFLDIVSAVYLEDADGIIVNLWGILDK (SEQ ID NO 212)>orf01246MEGVAKGRIGRKKNNGIDNRCCHKKRNGRVTWNLFFQKTIDDGDDSTFTRREKHTDEGPKKDSPPTISR EKMINLVRCDINFNQP (SEQ ID NO 213)>orf01249VDKTDEVSSKHCFEVVDKTDEVSSKHCFEVVDKTDEVSSKHCFEVVDRTDEVSSKHCFEVVDRTDEVSN RTTVRRS (SEQ ID NO 214)>orf01251MDYGLYHPCPIVTPSQSSSIVANPASKLISASEELIPDAIAVDFVEVNCY (SEQ ID NO 215)>orf01254MKKLFQEKFSKKPSHKEIERVQLGCAMMQATFHLMGY (SEQ ID NO 216)
>orf01261VVIGVASATTNIWIIFLSGFAAILAGAFSMAGGEYVSVSTPKDTEEAAVSREKLLLDQDRGLAKKSLYA AYIQNGECKTSAQLLTNKIFLKNPLKALVEEKYGIEYEEFTNPWHAAISSFVAFFLRSLPPMLSVTIFPSEYRIPAT VLIVGVALLLTGYTSARLGKDPTRTAMIRNLAIGLLTMGVTFLLEQLFSI (SEQ ID NO 217)>orf01269MLYVGIDVAKNKHDVTALNVPGKLFLNHSLFQIIKLVLNS (SEQ ID NO 218)>orf01296MDFEYFYNREAERFNFLKVPEILVDREEFRGLSAEAIILYSILLKQTGMSFKNNWIDKEGRVFIYFTVE EIMKRRNISKPTAIKTLDELDVKKGIGLIERVRLGLGKPNIIYVKDFMSIFQVKENDLQKSKNLTSEVKDFNLRSKE NELQEVKNLDSNYIENNKSKYSKREYSFGENGLGTFQNVFLAAEDISDLQIIMNSQLENYIRLPAKLES (SEQ ID NO 219)>orf01304LLHIRVCKTFDRIPYCMLALFLSKSIGLTILLHKVKTVIFIDDQSNDKTCKICIHISFFRIKLSQQCQL SFSVYF (SEQ ID NO 220)>orf01309MTQEDALIVISHIKVLSIVPNRCLKPLDKTFSLYNffIFLSQKYILLQANFLKISRVQLQ(SEQ ID NO 221)>orf01313VTTHDEPVYEKHGVLHYAVANIPGAVARTSTIALTNVTLPYIEALAGKGFAQAISEDEGLRQGVTTYQG YLTSLPVAQGLNRDYTDINDLV (SEQ ID NO 222)>orf01314VFFIDGFIVRCHTVSCFDNATLVNSNVNDTEPGRICLTISSVTNSGAFAPGMRMAPITTSASLILASML NELDIRV (SEQ ID NO 223)>orf01316MLIGIPKEIKNNENRVALTPAGVHSLVSRGHRVLIETNAGLGSGFTDADYQKQGAEIVATAGEAffAA ELVVKVKEPLSSEYGYLRDDLLLFTYLHMAAAPELADAMLAAKTTGIAYETVRDNQGQLPLLVPMSEVAGRMAV (SEQ ID NO 224)>orf01334LIRILGNSFISIDKAHEQAEEYGHSFEREMGFLAVHGLFTY (SEQ ID NO 225)>orf01383VILFFIRFRVSWLTYFIMSLIFIRFTILVCLIFTNMVASVTKAIILMADVRLDVRHST(SEQ ID NO: 226)>orf01387MIAMRSYITLICNLNNNLFCLNSFFLTNLVWSQIFSLLSVFITVYI (SEQ ID NO 227)>orf01388MFLFLAIDFIFYSYIFCMSLIFKVNIILSIYLNNISSLNLTDDILIFRLIVGGFH (SEQ ID NO: 228)>orf01390VIPR⑶HNHYIKVQTKGYEAALKNKIPSLQSNYQPGTFDEKAVLAKVDQLLADSRSIYKDKPIEQRQIELALGQFTESLKKIKVS (SEQ ID NO 229)>orf01419 MARLEPAKIAKIVLGILLYIIDLIKSSFVLPIPKAAKKSLILISFVPSFNDKNIVIRRPRQITKIMPRF ICFLFRIFACIS (SEQ ID NO 230)>orf01436MELSAIYHRPESEYAYLYKDKKLHIRIRTKK⑶IESINLHY⑶PFIFMEEFYQDTKEMVKITSGTLFDH WQVEVSVDFARIQYLFELRDTEGQNILYGDKGCVENSLENLHAIGNGFKLPYLHEIDACKVPDWVSNTVWYQIFPER FANGNALLNPEGTLDWDSSVTPKSDDFFG⑶LQGIIDHMDYLQDLGITGLYLCPIFESTSNHKYNTTDYFEIDRHFG DKETFRELVDQAHHRGMKVMLDAVFNHIGSQSLQWKNVVKNGEQSAYKDWFHIQQFPVTTEKLVNKRDLPYHVFGFE DYMPKLNTANPEVKNYLLKVATYfflEEFNIDAWRLDVANEIDHQFWKDFRKAVLAKNPDLYILGEVffHTSQPffLNGD EFHAVMNYPLSDSIKDYFLRGIKKTDQFIDEINGEFMYYKQQISEVMFNLLDSHDTERILWTANEDVQLVKSALAFL FLQKGTPCIYYGTELALTGGPDPDCRRCMPWERVSSDNDMLNFMKRLIKIRKYASVIISHGKYSLQEIKSDLVALEW KYEGRILKAIFNQSTEDYLLEKEAVALASNCQELENQLVISPDGFVIF (SEQ ID NO 231)>orf01442MGQEIKLIRKQFRSTRQEEKQIKEMMREQKVDSFSEFLRQNLLKKNYQDRIFESWFSLWQSQKFEQISR DVYEVLVVARENHQVTQEHVSILLTCVQELIAEVNQVQPLSREFREKYMG(SEQ ID NO 232)>orf01443MVYRYRTNLKKVFLTDPELHQLNERIAKSNCQNFSVYARKVLLNP匪SFVTINTDTYDQLVFELRRIGN NINQIARAINQSHLISQDQLQELSKGVGELIKEVDKEFQVEVKRLKEFHGSY (SEQ ID NO 233)>orf01444MVVTKHFATHGKKYRRRLIKYILNLDKTDNLKLVSDFGMSNYLDFPSHAEMVEMYNVNFTNNDKLYESR NDRQEKHQQTIHAHHIIQSFSPEDNLTPEEINRIGYETMMELTGGRFKFIVATHTDKDHVHNHILINAIDRNSDKKL IffNYALERNLRMISDRISKMTGAKIIEKRYSYRDYKKYKESSHKFELKQRLYFLLQQSKSFDDFLEKAKQLHVQIDF SQKHSRFLMTDRTMIKPIRGRQLSKRDLYDEEFFRTHFAKQEIESRLEFLLNRVNSLEDLITKAKELNLTIDLKQKN VTFILEENNQKISLGHQKISDKKLYDVKFFQDYFKNKEVVASEGLENLQEQYHAFQEERDKDKVSTEEIEEAFKTFKEK (SEQ ID NO 234)>orf01446VELAENQIEKLVDKGVYIKVSFGVKQSGLIFIPNYQLDIMEEENHKKYKVYIRETSSYFVYNKEWDNN CFIKGRTLIRQLSNDSQKLPYRRPTLKSLQEKISEINLMIELSNTNKQYQEIKDELVLEIAEIDMKLEETQEKIATL NKMAEVLINLKSEDHETRKLARYDFSKLNLTESTSLENVNEEIRVLQENLDYYLYEFEKRAIRLEIFVSTLNMEKDV FVIDKF (SEQ ID NO 235)>orf01447MAIIKKIVVLYGGLSEEREVSENSAKEISKSLLTLGYDVISIDLSQDCSYEIGEIEKSERGLNKQKVE IGSGIIDVCRKVDIVFLATHGGIGENGKLQAIFDVEKIDYTGNSFLSTAISMDKKLSKIVASSVGIKCASNLMVDR IQANDFPIVIKPIRSGSSKGIKIFQNKKQFDIYYKEHPELGSVFVEKYIKGREFSVGILGETVLPVIEIKVKNGF YDYNNKYTVGAAEEVVPAKISEKLTHTLQKSAYKIHKALGFNVYSRTDFIVDEKGDVYFIESNSLPGMTKTSLLP QEAKAAGIDFPNLCERIIELSREIRSQ (SEQ ID NO 236)>orf01449MKIINGICRYIFDSKGFATIEVEIFLDSGDTGIGAAPRGSTTGHYDIQYNEYYPRGNNFSPIPDGNIEFFNENILPRIINREVEDIEDITELDKHLFDIPEIENYGNVAIACSYAVWEAFSKNKKSPLWKLFFEPGSASKGKVKHL VNIIDGKPDSLLAGFEFLLVSEKEITFQSLLEISNIKNELMIKFKNQGFYTSISNQGALIINTDDFYIILDSLLETL KLYKNRYDIGLDLAMTDRYDSSLGIYKVPWCVSQQQTVTEIMDTYCDWGVKYPLVYLEDPFSDEDLDSWRKFQLIKP LKLQVF⑶DFYATNLERISQFKDCADGIVIKPNQVGSVSKTLEVMEYAEKSGISMAFSQRTAETENNIISHLAMSVT SSYLKAGGLDRLDRIAKYNEVLRNG (SEQ ID NO 237)>orf01450 MDNGKISTDGALVNNKNIEVNISSASIRYGISVFEAPKMFLLGSDIYIFRFQDYFNRLKTSCKFLNIE LPLDYNKLLYDIKKFIEFVPWQESYALRINVFCPYESELLGEVECALTLSYLDIGIRSKSGVSSKVIKRSNLIRTS NNNLYMIKSPSHYINARKELYSDIEFDDILYVNEKENICELSRSNIFLIKDRTVYTPDLGSGILDGITRKLIIDLC QEHNILIEIKELNYSKLSDFDSAFCVGTTNGITPIRNIDKNIHFDTNNLLLAEIVNYYKEVFSKKGVEKYKEWFVKL (SEQ ID NO 238)>orf01451MIKDVNYFNERAQIIRRTINDMIFGAESGHFGASLSSVDFINVIYENYVFPENAEFILSKGHAAPALYA KLIESGVLDKDFIYGFREYRSLLTGHPNHRIPTLKFGLGSLGQGPSIGVGMAWVNKRKKSDKKIFVMLGDGELNEGQ VWEAFYTCRNLNLQNLVFIIDRNFLQLDGKCEDVANFPNLAQKISSFLGTNPIEVNGNSYDEILNVLDNIDYSQTNV IISNTTKGKGIEFMEGKTEFHSYNILSSEKEVLYKRAMECLG⑶KMA (SEQ ID NO :239)>orf01452MRKTFIDELINKNIEEQNIVVLTCDVGRSTYASKFKEIFPENYLNLGICEANIVGISAGIAGTLEFVP FVMLFSKHLILRALEQINDSILMNKKKVILVGGYSGYSASKEGETHQLLNDISILSSFPDISIYCPYDQSSIQTAI NESINNDYSSYIRINKNKILNDVVSRYISQGNKSIIISMGYLGSLLSKKYMEDSDIREFADFILVSKIKPIDWEY WENFLRKYETVYIIEENTLTGGLGEQFKNYFFGLGINIISFGIKPHFGETCDYETLLTNEGLSPDKIFEKIRRIN HVQSSEKSIffR (SEQ ID NO 240)>orf01453MYNLVKRVFGDDNFVKSDGIYLYTDDNKEIIDSCSNSMNVNLGYGVLEIEKVIHEQIRKINFMHTGKGT TYESLMLANRLHDIIKPYGNYKVYFATSGSDCIEAALRISVLYQQKNKRNQESNTRFATFEGSYHGSTLGALSVSGH RKFQKLYNGYIGNCLTIPTRWNLEWEMDFTDITAFVLDSMITNPIGSEMIDRDYLNYLVQICKESGVITIIDEIATS IGRLGCFFGFEDSGISPDIVCISKGLGVGYANIGAVIVKSNIIDSINSADILGHTYNASPIDCKIAMTVLDYIEEHG IFEHVNNLSNYIEYRLKVLKNKLPCISKVSGKGFMWSIHFRNNVNASKVFKQCYNNGLLLLYLEYEEYNHMTFCPPL ITSKNQIDSMLDILEKSITEVLHGY (SEQ ID NO 241)>orf01455MDIKKLGFIIITNETFAFNLVEEVVEKLSILDVNRAIIKLLPKVDETTLIKHYREHLINWNGKEGKSQV PSLGWPAVRNRFSSSVVLILLEGNKQSLSDEILQIKGNTYPERCRQNQIRIKGFNPTYNLMHSSDSAEEALKEAELY FSKKELESFFCGEIGITFEEILNFILELDSIQKGGIRSNSDLENKVNKMCYWKQRIFDLFSSKTKEESRKISEELNF IKSNRSPEDVILYLENESILWSKLERDLYLSHLIIEEISGE (SEQ ID NO :242)>orf01456 MVKIYEETLRDGIQSSELSMLNTEDKKKVIKNFDNAGIEGCCIGFINSSKKENDEINELFQFIITNKLK IVPAVLCRLLIEDFKEIKNIVQCNLFNQLKVYTYIAVSPIRMKVENWSEEIIIEKIIDFLNYCQMENAKITIAFEDA SRADKSFLKKLIEIINNYPLVKSVVIADTVGTCNYNSTRDLVYFFRKNLFLSKTIEWHGHNDLGLAVSNALSAIESG ADIVHTCTLGIGERCGNTSTEQLIINLIVSECGRRATYKLRYLYDVAKILENKSQFPISPKTPCFGMDSFFTCAGTHASSLYKSYLKNDNNFSIIFSPYDSNIFGREVTVGINSQSGRSSIEYISRKYGLELSQENITSILGLVKQNDLFFREE EFVDYVKQKRVERLDYK (SEQ ID NO 243)
>orf01457MLNKKEffKDLTISKSENDSIISCLYNWGFELPKSKDYTFSLTWYGYNNVSYKYCEKECLTLGELSLLFP QLNDLFffENQKDNIEGRRNFYKNCKNLLGKFNIYSVRDILEISDRDLQFALTNRVGSKEFENSIVSLMYINKLSDDN KAENTLEKKLYFSINNEDSIIPYYENTLGMTAGNYYFTASHRTFFSSTFPDFFKIDVPYKISNSVRNLTRNELRIRA SEIIKSELANSENPILKIFDDYAYVRIGKRNMVLRNKFFNGFIAPLFAFFQQRIFDNGKSFFTHFYDLRKNTSQNIP DYLLLNILFPLIDCFEFFLNVSIKYKRLIFPYDFHMQNIMISIYDNQIGFIFQDFDMSKELTVTSFYEQLDFFFEKF VVTNILESINELKLDEKKYIMREMKKIINTKIIIKAESYFGFPSPSEVIFPDFMKQYLRENQNVKERTIKYRSYLR (SEQ ID NO 244)>orf01458LFIDILKKKKMKIIEAHDALSAYIIDQTKYSADK ⑶ IFEYDGIWISSLCDSIIRGKPDMEWNITDRLQ TIDDILCVTEKHIIVDIDSGGTLAQTASLIEKITLRKIAGIVIEDKIGQKYNSLFGEKNTQLQDSTESFERKIRVAI KSRKNSKTAIIARIESLVLGKSLEDLLYRGNCYIKSGAEALVIHALNSRLDDLYQALKYFKRYFPEIPLIVIPTDFP YVCAEELFESGADLIIYANHLLRSIIKPMEYIAKSILIDGYSNGVENKLLPISEILNYIPLLEEIDEK (SEQ ID NO 245)>orf01459MKSKDLISSLKLNGVTRFFGVPDTFLYPITSQLANDELIIVPNEGNAVSMAFGYSITTSRMPVIFLQNS GLGNILDPVQSLVGQAVYNHPMLYIIGFRGGTDDAPQHSECGKVTKKLLEISQFDIYEKDYFTNALDTDIRRIIDNI KKKNKSAAILVDKEFFSDIVNIKNYQISDYNDILNKICAVLEKEKDSIVLTSTGYITRHMENVKDTYKKNFVHIPMP GSLGQTISFGAGICMGTSINNKKKKIYIIDGDGSLFMHMGSLALFDYYNLDVTYILLNNYKHLSVGGENTLASSCNF FKLAESMNFDNIYSSDNLEVVDFEEKLNQQGKNFIEIICSNEVTYSLLERMDFNFEEIKQFNMEN (SEQ ID NO 246)>orf01460MPDRYVEYSQNDYDNIMKLDTLFISQLDSKYKVEYHKLPSLISGEVLKRCGYFSTMPNQLSKVDIIDVS QLESLGNNRELEEIKYSSSENYFLTPAACLHFYPMLEHKEVKECIYSSLVDVFRYENGNFTMGTRQWEFTVREFLAI GNPKFVEEFLEDLKEKFLTIALRFDSTAKIQNACDNFYPTNLNKVKQKFQKYNNLKFELIVHISEKEVSVASFNYHN NHFSKEFNFDSNDTIVTGCVGLGIDRWISLIKESEKDYKL (SEQ ID NO 247)>orf01461 MRKQIISLFHAYLNENTQDWVEIDENFLLYQHLDMFYYYLCKKNNIEPPLMEKFEVRKKVIESRNRQYI KVARDLNAIFEKQSIQVAFLKGIQTSEKYYEEPffIRYYSDLDILVAREMIPGVEKLFYQLGYVFGHLKDNGEIHHAT REEILYQKLFTHEIYNLVKKENDNVFINVDINFLFSWKGLSDSEIEFNDIKNDIIYDSKIKINTLDKVMNFIHICCH LYNEARYFALNRSFLGGDPREIQLSRVFEIALILKDLKQEEFNSWYSSRKLNCDNKVFASIGVTKQLLELNLSILD NYTEELKVKDEFNSYIDKDQKVKYWPISIEDRVFDLKLKVKTCDKIFIN (SEQ ID NO 248)>orf01462LKYDSEIKNVIKDYIDFEFDINEIDNNVALTDYGVDSLKYISIILALEDYFKIEIPDNYLVFSKSNTIK KLNSIIEELL (SEQ ID NO 249)>orf01463MKYINSSLKPVDNYYSLEEVTCFDRLLGIFLNSINNSYCDLFYMINNFYRCYKVDDSKNEYDFEREMHILRNFFCIESEKINFSDEYVLTEFIVKNINKYGSVFVPINLKEIYYSAYYKEQDWPHLFLINGYDKEKELFYVIDATQ IYSDILTEQNFCITFEILERAYKSYFHQTILNKEKEYIFVVTTVVNELTETEIFHETFKYLFNQSSISSRELEIVYK ILTNRDFTLLANLKNITKKKKLFFTIFFEKLRVYELISNKELLYLSRTVETILEEffTIFINRCIKNILKNDTKLVNY DFFVLEEKKIFDFFSKQASRYKERLFEIISSNSNRYNEVFECIQNSGKIITITEDNSRKFRFSFIGDKIYNSWFNDD SPKVRINQDLNYLIVKINVIHKEKDSKFVAGLYCFIDDNLYYFGLDSNYFINLDLMGKTPEIFRKRLETSEVYLKIS RQEDSCKFSYSVDGITYFYATSLDIRSCHFSCGIGCKTYSKPTPLCIDFEDLLIG (SEQ ID NO 250)>orf01464MAMIEVSCLRKDFVKIIKEPGLKGAIRSFIHPEKQIFEAVKDLSFEVPKGQILGFIGANGAGKSTTIKM LTGILKPTSGFCRINGKIPQENRQDYVKDIGVVFGQRTQLWWDLALQETYSVLKEIYDVPDAVFQKRMDFLNDVLDL KEFIKDPVRTLSLGQRMRADIAASLLHNPKVLFLDEPTIGLDVSVKDNIRRAITQINQEEETTILLTTHDLSDIEQL CDRIFMIDKGQEIFDGTVNQLKETFGKMKTLTFELRPGQNHWSQFVGISDIHVTRKELLLNIQYDSSRYQTADIIQ KTLSDFAIRDLKMTDVNIEDIIRRFYRKEL (SEQ ID NO 251) >orf01466MVKLWKRYKLFISAGMQELITYRVNFFLYRI⑶VMGAFVAFYLWRAVFSSSHQSLIRGFSLSDMTFYII MSFVTNLLTKSDSSFMIGEEVKDGSIIMRLLRPVHFAASYLFTEIGFRWLVFVSVGLPFLIIIIGLKLLSGQPILQI SLMTLTYLLSLILAFLINFFFNICFGFSAFVFKNLWGSNLLKNSLVAFMSGSLIPLSFFPKIIADILYFLPFSSLIY TPVMIIVGKYNISQMIQAVLLQLFWLLVMIALSQIIffKRVQSHITIQGG (SEQ ID NO 252)>orf01467LLVGISLLSATVTSLTWTWTKVFIFLISIPFATLIYTSLKIATASIAFWTKQSGAVIYIFYMFNDFAKY PVVIYNSFLRWLISFIIPFAFTAYYPASYFLKDKDGLFNIGGLILISLIFFTISLKLWNKDLDAYESSGS (SEQ ID NO 253)>orf01468MDEVFKFYCTNIIRVIFIKWLFCLKSMNHTNLTLVTTTFKQFNSTSLGNHHAMV (SEQ ID NO
254)>orf01469MQAFDGSTEFIHNGKGEKDSSKYQINGAGRCEVPVYVPKTDffDffIIYPQGIYD (SEQ ID NO:
255)>orf01471MRVKRDYPNYKIYITENGLGYKDEFVDNTVYDDGRIDYDYVKKHLEVI (SEQ ID NO 256)>orf01472MEffIINIIRGIRYIGREAGVTFVEPSQTSIKSFDITIL (SEQ ID NO 257)>orf01473VRHYKDYISQRSDWELAGIYADEGISGTQVGKRQDFQRLINDCVNGEIDYIVTKAIARFARNTLDTLKY VRMLNDMQIGVYFEEENIDILTMDGELLLTILSSVAQQEVENTSAHVKKGLKMKMERGELVGFQGCLGYDYDVETKQ ISINKKESKIVRYIFERYLEGIGGKVIARELDELGYKSPRGLEHWNDTTVLGIIKNEKYKGDILIGKTFTVDPISKR RLSNFGEEDKYYIKDNHEPIISK (SEQ ID NO 258)>orf01474MYAFSSMLECGFCGSILSRRSCHCRSDYRKVVWHCVTSIKKGKKFCKHSKGLEKLAIEGAFMEAYRQLY HSNENLMTDLLETIESELNDNSLNKELKRITNKLRTLLKKEENLVNLRLEGKISDTIYDEKYNEISSEKEFLAEEKVNIETTLKSEIDVKKRLTEFKHLLSSQKMLTEFDRAVFESIVEKIIVGGVNSNGEIDPAMLTIIFKTGETQNKDGKQF KSKRKNAKLETDKLCPQNSDEDKKLYSQGTDNTRGVCSVAGSILVSQ (SEQ ID NO 259)>orf01475MGGNPPIKKYSIVDKIVLSTKIKRIIIFTVFRENWEPYMKKYTEVFQSQFPNLNIDYLLLDTEQIDLDS YLDADLIIIGGGNTEKYIATYVNQEFKNYIDHMLNKGAKVIGFSAGALLLGEKVYVSPNDNSDHQIKIKDGLGLFSQ FLISVYYDSWNDKANKDRAEELVNVPIIPLNDHSCLVLDKLGNIIEKID (SEQ ID NO 260)>orf01476
MDFSSKIAINTGWSDDKKYCVTDQNQQKYFLRVSDKEKLDSKKFEFDMMGKVASLGVPMCKPISIELCD DEVHSLHEWIDGRDAIDSILTYSENQQYTYGVEAGKILRKIHTIPATEVCEDWEIFFNLKIDDKISNEMIW (SEQ ID NO 261)>orf01514LCSALKNSYDIELIKVLSNKAHLYLPIETVTPQTVSTS (SEQ ID NO 262)>orf01537LVKNPFIEIERIERTWLTAHLYRKFDKYFHKTRPPIKVFEHLIGGLFIMKTFT (SEQ ID NO 263) >orf01538MIKIYFTKFSENHNPFCKIFEIIFTSLIFQSILNKNKKNPLHQGETNVV (SEQ ID NO 264)>orf01545MSQVKGLCVLDVDGTLILEEVIDLLGREAGHEAEISQITSRAMRGELVFESSLRKRVSLLEGLPILVFD NVFNSIHLSLNVPEFISILQKNGILVGLVSGGFTPIVGEISKIPWYCLFHCQPA (SEQ ID NO 265)>orf01546MLKSAELGIAFCSKEMLKKEIPHHVDKRDFLEVLPLIDCLE (SEQ ID NO 266)>orf01551MFGNWFFKAFVCSLERLAQDRTMNWFSCIGNKNTVAFVPILIGCFA (SEQ ID NO 267)>orf01565MEKYFGEKQERFSFRKLSVGLVSATISSLFFMSVLASSSVDAQETAGVHYKYVADSELSSEEKKQLVYD IPTYVENDDETYYLVYKLNSQNQLAELPNTGSKNERQALVAGASLAALGILIFAVSKKKVKNKTVLHLVLVAGIGNG VLVSVHALENHLLLNYNTDYELTSGEKLPLPKEISGYTYIGYIKEGKTTSDFEVSNQEKSAATPTKQQKVDYNVTPN FVDHPSTVQAIQEQTPVSSTKPTEVQVVEKPFSTKLINPRKEEKQSSDSQEQLAEHKNLETKKEEKISPKEKTGVNT LNPQDEVLSGQLNKPELLYREETIETKIDFQEEIQENPDLAEGTVRVKQEGKLGKKVEIVRIFSVNKEEVSREIVST STTAPSPRIVEKGTKKTQVIKEQPETGVEHKDVQSGAIVEPAIQPELPEAVVSDKGVPEVQPALSEAVVTDKGETEV QPESSDTVVSDKGEPKQVAPLPEYKGNIEQVKPETPVEKTKEQGPEKTEEVPVKPTEETPVNPNEGTTEGTSIQGAE NPVQPAEESTTNSEKVSPDTSSENTGEVSNKPSDSKPPVEESNQPENSGNTTSENGQTEPEPSNGNSTENVSTKSNT SNSNGNEEIKQENELDPDKKVEDPEKTLELRNVSDLELYSLSNGTYKQHISLEQVPSNPNSYFVKVKSSSFKDVYLP VASISEERKNDKILYKITAKVEKLQQEIESRYKDNFTFYLAKKGTEETTNFTSFSNLVKAINQNLSGTYHLGASLNA NEVELSTDDKSYIKGTFTGQLIGEKDGKHYAIYNLKKPLFESLRGATIEKLSLKNVSISGKDDIGSLANEAQNNTKI KQVHVDGVLAGERGIGGLLAKADQSSITESSFKGRIVNTYETTASYNIGGLVGHLTGSKASLTKSKATVVISSNTNS SDQTVGGIAGLVDKDAHIQNSYSEGDINNSQRFGKVAGIAGNLWDRESNSENHAGRLTNVLSDVNVTNGNAISGYHY NGMKITDAFSNKANKVFNVTLEKDEVVSKESFEERGTMLDASQIASKKAEINLLTPPIVKPLSTSGKKDSDFSKIAH YQANRALVYKNIEKLLPFYNKATIVKYGNLVKENSILYQKELLSAVMMKDDQVITDIISNKQTANKLLLHYKDHSSEKFDLRYQADFAKLAEYSLGDTGLLYTPNQFLYDQDSIINQVLPELQQVAYDSEAIRKTLGISPEVKQTELYMEDQFT KTKQDLANSLKKLLSADAGLA⑶NPVTRGYLVDKIKNNKEALLLGLTYLERWYNFSYGQVNVKNLVMYHLDFFGKGN TSPLDTLIELGKSGFNNLLAKNNVDTYAISLASHHGTTDLFSTLENYRKVFLPDKTNNDWFKSQTKAYIVEEKSNIE EVKTKQGLVGTKYSIGVYDRITSDSWKYRNMVLPLLTLPERSVFVISTISSLGFGAYDRYRNKEHQAN⑶LNSFVEK SAHETAERQRDHYDYWYRILDEKGREKLYRNILLYDAYKFGTDHTEGKATEVANFDNPNPAMKHFFGPVGNKVGHNG HGAYATCDAVYYMGYRMLDKDGAITYTHEMTHDSDQDIYLGGYGRRSGLGPEFFAKGLLQAPDQPSDATITINSILK HKTSDSTEGQRLQVLDPTTRFNDAADLQNYVHNMFDVVYMLEYLEGQSIVKQLDAYQKMTALRKIENKYVKDPADGN DVYATNVVKNLTEDEAKKLTSFDSLIDNNILSAREYKAGTYERNGYFTIKLFAPIFSALSSEKGTP⑶LMGRRIAYE LLAAKGFKDGMVPYISNQYEEDAKQQGQTINLYGKERGLVTDELVLKKVFDGKYKTWAEFKTAMYQERVDQFGNLKQ VTFKDPTKRWPSYGTKTINNVDELQKLMDEAVLQDATGTRWSNYN PEIDSAVHKLKRAIFKAYLAQTNDFRSSIFE NKK(SEQ ID NO 268)>orf01580VLGGRANSVTSCTTNSHWNLTFTTKHVTCFSSLVDDIVHGNNREVHEGHIDDWTKSCHGCSCCSSRDGS FRNRTVTDTFWTKFFKHSNRSTEVSSEDTDVFSHQEHIFIATHFLRHSKDNGVTEGHCFCFHFISFSLVCVNIFKG (SEQ ID NO 269)>orf01581MDMFYIGHFLDIRRDTVTVVNAIENDWQVPDRSHVHCFVENTFIGRTISKEADNDFTGILHLLTEGCTD SDPHTTTYDTIGTKVPSIKVSDMHRSTFPFTGSSVFTKDFSHHSVEVNPFSNSLPVSTVV (SEQ ID NO 270)>orf01602MKINKKYLVGSAAALILSVCSYELGLYQARTVKENNRVSYIDGKQATQKTENLTPDEVSKREGINAEQI VIKITDQGYVTSHGDHYHYYNGKVPYDAIFSEELLMKDPNYKLKDEDIVNEVKGGYVIKVDGKYYVYLKDAAHADNV RTKEEINRQKQEHSQHREGGTSTNDGAVAFARSQGRYTTDDGYIFNASDIIEDTGDAYIVPHGDHYHYIPKNELSAS ELAAAEAFLSGRENLSNLRTYRRQNSDNTPRTNWVPSVSNPGTTNTNTSNNSNTNSQASQSNDIDSLLKQLYKLPLS QRHVESDGLIFDPAQITSRTARGVAVPHGNHYHFIPYEQMSELEKRIARIIPLRYRSNHWVPDSRPEQPSPQSTPEP SPSLQPAPNPQPAPSNPIDEKLVKEAVRKV⑶GYVFEENGVSRYIPAKDLSAETAAGIDSKLAKQESLSHKLGAKK TDLPSSDREFYNKAYDLLARIHQDLLDNKGRQVDFEALDNLLERLKDVSSDKVKLVDDILAFLAPIRHPERLGKPN AQITYTDDEIQVAKLAGKYTTEDGYIFDPRDITSDEGDAYVTPHMTHSHWIKKDSLSEAERAAAQAYAKEKGLTPPS TDHQDSGNTEAKGAEAIYNRVKAAKKVPLDRMPYNLQYTVEVKNGSLIIPHYDHYHNIKFEffFDEGLYEAPKGYTL EDLLATVKYYVEHPNERPHSDNGFGNASDHVQRNKNGQADTNQTEKPQTEKPEEETPREEKPQSEKPESPKPTEEP EESPEESEEPQVETEKVEEKLREAEDLLGKIQDPIIKSNAKETLTGLKNNLLFGTQDNNTIMAEAEKLLALLKESK (SEQ ID NO 271)>orf01625MDESFDDIAHEQFTSNLTTKTDNVGVQLFFSIKGCCHITNQGRANTWNFIYSVVDTNTSTTDTYSKISL AASYSFPYFFTKDWVVSPCMVICTKVNDFISF (SEQ ID NO 272)>orf01629MLDFQDRSPffLEGQKEIDLSYDLFSTDAVTLDELQSRTIALRSLKHDKGLKVHFAEFPNLIIWSTLNKG PFITFEPWSGLSTFLEEGDHLEDKKNVCLLEANQVEELGFEIEVL (SEQ ID NO 273)>orf01634MKIKEQTRKLAAGCSKHSFEVVDETDEVSNHTYGKATLTWFEEIFEEYKN (SEQ ID NO 274)[1013]>orf01643LIESQVFSSLQVCCLNLCHLKFQHFDTCLVFLLVFLDFQNLLAHFPIGIKTRLIGFFQVPKSGITKFIQ HLDMQLGTH (SEQ ID NO 275)>orf01644MVMLTMNIYKMLPNSSQNRQINHLTIYTADTTTILQDFPTDDNFIT (SEQ ID NO 276)>orf01645 MTNNICRRTSSQHHIHGINDNRLPCTRFTSQDSHPLFKIEGNSLNNGKVFYRNFK (SEQ ID NO: 277)>orf01656MPHTRDNWQTRFKNSSYHNFFVKGPEILNRTTSTTNNEQIQIVPLISTRNISSNFLRSPFTLNLGRIK KDVNTffESPADGRDNISNNGSTTAGYYTNSLRKLGQSLLEAFLKQAFFCQFFLKLFKLNRKRPNPIRLSFFNDDGV ATTffFIDLYTPNHIDLHSFFQVKP (SEQ ID NO 278)>orf01660LAIIRNRTCSLKLINGHLTFWTLHFLTSTRILIELATINLNCRIHRGNLGNRPSQASNRFINKLFIQG RQNRGFCDHFPTSILSRRGIAQSNFPLIDLTLVLHKLDHACRLANRNRQNTHHIRIQGSTMTNFLGSQNLTQFKNR IMRGHSCFFF (SEQ ID NO 279)>orf01667MFALRKPGNIYTRITNPTTAALEGGVEALATASGMTAVTYTILAIAHA⑶HVVAASTIYGGTFNLLKE PLPRYGITTTFVDIDNLEEVEAAIKDNTKLVLIETLGNPLINIPDLEKLAEIAHKHQIPLVSDNTFATPYLINVFS HGVDIAIHSATKFIGGHGTTIGGIIVDSGSFDWTASGKFPQFVDEGPSCHNLSYTRDVGAAAFIIAVRVQLLRDTGA ALSPFNAFLLLQRLETLSLRVERHVQNAETIVDFLVNHPKVEKVNYPKLADSPYHALAEKYLPKGVGSIFTFHVKGG
eaearkvidnleifsdlanvadakslvvhpattthgqlsdkdleaagvtpnqirlsiglenvedliedlrlaleki
(SEQ ID NO 280)>orf01668MTRDFKFETLQLHAVQVVAPATKSRAVPIYQTTFFVFDDT (SEQ ID NO 281)>orf01672MSQKKNNKKKNKRKNLLTNILAGFLILLSLALIFNTQIRNIFIVWNTNKYQVSQVSKEKLEENQDTEGN FDFDSVKAISSEAVLTSQWDAQKLPVIGGIAIPELEMNLPIFKGLDNVNLFYGAGTMKREQVMGEGNYSLASHHIFG VDNANKMLFSPLDNAKNGMKIYLTDKNKVYTYEIREVKRVTPDRVDEVDDRDGVNEITLVTCEDLAATERIIVK⑶L KETKDYSQTSNEILTAFNQPYKQFY (SEQ ID NO 282)>orf01679MRWNIGCHPNRDTSCSINQKVWKTRWQDQGFPFIGIIVINEINCIFVDITKHFQSNLAHTCLGITLSGS TISIHGTKIPMTIYKHVTVAPPLSHTDHGFINRGIPVffVIFTHDIPCNTSRFFMGFVWGHTQFIHSVENATVNRF (SEQ ID NO 283)>orf01683LKKKffFFADYYDTTIILLALISVILVLLGFAEMIDLDNPPYSIIDLVIWGVFVIDYSWRFFITKRKffRF ILENIFDLLAILPLNAIFTVFRLGRIFRLVKLTKLLKLTRLLRIIGLTGKLERKISRFLRTNGLIYILYVNIFIILV GSSILSWEEKSFSDSLWWALVTVTTVGY⑶IVPVSLLGKWLAVLLMLVGIGTIGMLTSALTNFFVKDNPDEQIKLD KLKDELSS (SEQ ID NO 284)[1033]>orf01693VVDFKQTRQDPHDITIYSWLRQVKSNTGNGSCCVRSNPFQAGNSFIGIWKLATKVSHNLLGCSLHIANS RIITQALPSFQ (SEQ ID NO 285) [1035]>orf01698LINSQLIPLVQVVVNQGRKGIVGSCNSMHISSKVEVDVFHWQNLCIPTTSSTTLDPHDWTKRRFADSN HGFLANLVQGIRKTNGKRRLSFTCRCWVDGSNQDQFTDWIALNCTNFIKAEFSLVLSVQLQIVVRNTKFLYNINNW LQLNTLCDFNICFHSKFL (SEQ ID NO 286)>orf01711MLFIIGHLNFPTAGSFIDSTLHRLGNRVCIHDDMAFTVTSSTSNSLDESTFVAKETFLVSIENSYEAHF RNVNSFTEQVNSDQDIKDTQAQVTDNLRPFQGLDIRVHVLDLDTHFLEWGQILCHFLGQSCDKGTLIFFNAGIDFT QEVINLSHSRTDFHLWIQESRWTNDLLNHCLGLFIFIVTRCR(SEQID NO 287)>orf01712MNVTLKLLPTERTIVQSRRQTETIINQHFFTRTVSIVHALDLPYGHMTLVNHNQEIIWEEVEKRIRRLS FAPSIHVARIIFNPIGIAHLTQHFDIILCPLFQTLGFKQFTFLFKDS (SEQ ID NO :288)>orf01713MIHFSQHLTCQSLNFTNTVNFVSKKFYSKGMFISGSWENLYHIPTNAKSSALEINIIAFKLNIDQVIQE FITRNL (SEQ ID NO 289)>orf01714VAKLVNLVIDRTILLNIGIARRDIGLWLVIIIVGYEILNCIFREKFLKLPIELTSQSFIVGNNQSWFID FRNDLTHSIRLPCSSRPHQNLSFFSPLNVIHQLLDSLGLIS (SEQ ID NO 290)>orf01734MNITQTDFLAVNLVFAISTTIDMAFHPDFLTCILDKSVMIIQSHNYRSIIERFATFGSSKDDIRHLAPT ETLDTRLPQSPTQTFCNIGLSRSIGSNNCRHTLVKNDLGLISKRLEPLNFDFL (SEQ ID NO 291)>orf01736MGFIVCNHLKLACFNLRNHDLIDKFLDLGHILIQKKGTKKGFKGITKNGVTIATTRFFFPFTQLDKLVK LAITRKTS (SEQ ID NO 292)>orf01748LFTCFSKLDNKTASTTYISHKFFTAIPVCFEFFKGFWFPRKDTTKKNIFIPMFLVECFNFWVELR(SEQ ID NO 293)>orf01753VVRELTGEIYFGDHILEERKARDINDYSYEEVERIIRKAFEIARNRRKIVTSIDKQNVLATSKLWRKVA EEVAQDFSDVTLEHQLVDSAAMLMITNPAKFDVIVTENLF⑶ILSDESSVLSGTLGVMPSASHSENGPSLYEPIHGS APDIAGQGIANPISMILSVVMMLRDSFGRYEDTERIKRAVETSLAAGILTRDIGGQASTKEMMEAIIARL (SEQ ID NO 294)>orf01754MAKKIVALV⑶GIGPEIMEAGLEVLEALAEKTGFDYEIDRRPFGGADIDAAGPPLPDETLKASREADAI LLVAIGSPQYDGVAVRPEQGLMALRKNSIFTLIFVL (SEQ ID NO 295)>orf01758LANIESHCNFFQSSIFSSLPNTIDSLFNTSCTILDSSKAICHCHSEVIMTVRRIDDLTIRLDILNQVFEDGTTFLffCGKSYIF (SEQ ID NO 296)>orf01768MPRNRFSFTVRVTREKNFISFFSFFFQVIDKRAFSSDIDILRFIIIFNIDGHTGFLQITDMPDTG (SEQ ID NO 297)>orf01772MKIKAQTRKLATGCSKHCFEVVDKTDEVSSKYCFEVADGS (SEQ ID NO 298)>orf01781VHAHTDKLCNGCNRIFNSIISHHTIFRERNKLSHKAIKSTRQEMGPCHVVFIEFFITLHRRLIGNHDNF LTNLVGSGRVRNDGST (SEQ ID NO 299)>orf01782VNHCHWKLFIQNLGITFSLIVTLIRMTDSHVVGTDKDMILLVNSLFLIFDIDKLRLS(SEQ ID NO: 300)>orf01784VGNNDILWSKRTISINGFNDFLNTCIAVSTTLCNDDTFLIKRKIFIYKIFCMRNPVSMNTNYNFFNTWL QDKFFNCMNQNRSIT (SEQ ID NO 301)>orf01794LVAPVASSTRFFKNNDSLTSWNNGFIIITINTIISYQRISKGQDLSIIRLVCNGFLVAGHPCIKDDFAC YINICSEGLAFKNCAIF (SEQ ID NO 302)>orf01796VVCYFYITIDWSWVHEDCCFFQTIVTFLSQAMLGMVVFF (SEQ ID NO 303)>orf01797MAFVLHTEKHHDINLINDFINGYKLSIVCKLLTSPFLRSREKEFSSQAFQNLHIGFGNA(SEQ ID NO 304)>orf01798VVQVTCNSNFKTLKVAKFLINGHQIKQALARVLARTISTIDDGSRNRWTSNQFSIVVDLWMANHTDIHS (SEQ ID NO 305)>orf01799MCPCRILKEEIGNNRMVFIGNLGSIFKLNSSLDQFHYLINSEVFHGHHMVQCLLIF (SEQID NO 306)>orf01824VQFHLIIFQNLFCSLDIVIDSLTTNTKLLSYLSKTVIISVVKLYIIHLLICQKRRIKFKERIHTIGFFD SKLTIXXXFHSLIN (SEQ ID NO 307)>orf01826MHFHIIKLVNHFQLLIKLNRISHPNLHIKSSFLSLVLLFYQKEQDFAIMVI (SEQ ID NO 308)>orf01840MTGKKGFLFLNCHICMVTTTTCFLKERVESELLIFFYISPNRCLITV (SEQ ID NO 309)>orf01843LNRSILDNITLKHEVTSQKIEEVCKAVQIYDEIMAMPMKFNTIISEMGSNISGGQRQRIALARALINN PSIVILDEATSALDTINEERITKYIKSQGCTQIIVAHRLSTIKDADIIVVMKGGKIVESGNHKYLMDLGGEYYSLYTKRK (SEQ ID NO 310)>orf01845LFKGGVTISRTPLSSEDTVMIDATEVKINRPKKKTISE (SEQ ID NO 311)>orf01848MAGKKDFLFLNCHICMVTTTTCFLKERVESELLIFFYILLNRCLITV (SEQ ID NO 312)>orf01850MYQDEAGFGRISKLGSCWSPIGVGPHVHSHYIREFHYCYGAVDAHTGESFFLIAGGCNTEWMNSFLEEL SQAYPDDYLLLVMDNAIWHKSSTLKIPTNIGFTFIPPYTPEMNPLNKCGKRFVNVDLRIRPFELWKMS (SEQ ID NO 313)>orf01852LLQSPYAIDTINLKKDFLEKPIDIEKFKAFLEKEEIPLAIAWQ⑶SLHFYTKDRSILDNHLDHLLEKMV NDPEKLSDFSMDKSLDDTIDEAKSQITFK (SEQ ID NO 314)>orf01853MKVVNLYDLKQMGNKGGCTIQLIHHFPFGMGLGHLKKDYIEFKRVGIFDGKAVEVTLREPYSRDILQVV KSIKQRQKLIAYRYKEGKLLFVKKEV (SEQ ID NO 315)>orf01876MKPSGQEFPHPIFYSLFCFYTDTLGINSQVMQFSFERLLFQFCLNCWHLVMRSQNHNCRPSTRKVGC IGPIFFGHLLNHRKFSYQVLTIALMEEISLDCLPSGHHVSCQQGSNRYIGDRTCSNSFLIRQFFRQDTTAVAST (SEQ ID NO 316)>orf01878LQVWYNLQSDFEQEITLIMWNPFANLVFNQPLISFFADLNLKILGYSYTDRVKTWPDIGTGCRYNNLHL ILLAP (SEQ ID NO 317)>orf01909LRQNRCYNCFHDHSCSWKSSRITSLHGCLVRFVGFDIHTHKRFIKSRNGFHDPTNNDGLPISHTTFKTT (SEQ ID NO 318)>orf01910LAAFTITSLKAKTKFHPFKGIDRDNSLSQSCIQFSIPLDIGTKTNWNASDDCLHNPTDGITITFDLVNI VLDFLFSFLVDNRNFRLGSSLLNFSDCQIFRNIDFLATKDHDMVGNLHIQLSQETFGYCTNCHPHGGFTS (SEQ ID NO 319)>orf01911MTffARMSNFPLAFKAVFNVLRRHDVQPFLVVLIDDIHSNRRPCRLPVANARSKDNLVILNLHTTTTTVA TLTASKVLIDILSCQWKSSWNSLNNSC (SEQ ID NO 320)>orf01913MHDLAITGSRFDGMANSVAKIEVKTNTIVQLIFNHHLALHLTRMFNQGLCMFQNTLNRTIQSRQE SPQ FfflLNQAILDNFTHPFNQLSFSEGFKNKWINQNPIWLGKGPHHIFSKWCVNTCLSTDRRINLSCQTSRNLNKVNTP HIGRGYKSSQVPNNATTKSNDSIATSQTLLD (SEQ ID NO 321) >orf01915MVICHNDYLLRLPEFSQPLTSLGHTTFFNLNIIRMMRNIDSDFHRRVSLSLLVFFC (SEQ ID NO 322)[1109]>orf01920LIEGHLVFADKPAQALVLLRKVGSPKKVSFLTLHLYFLILKIDILKITGF (SEQ ID NO 323)>orf01951MAVTKSQVFSRQGFDFSILGQDLTRLQDVSNLATIGTRIHKDSTANASWNTTSKLKAS(SEQ ID NO: 324)>orf01952MTEGNASCFNQVSPSFCFNGIAINRNVIELVTQDDKSTNPTITNDDIACIAKNHPRDIFLVGKFHNASQ LKTISffKDQ11SLSTYFCITIAMQGFLKTDINSF (SEQ ID NO 325) [1115]>orf01965MRLRDLRRVDFPDPDGPIKAVISLGWKDRETLFKAFFLL (SEQ ID NO 326)>orf01968LKNHSNVFTHFINVDFWTVDINSTIENLPSYFSNINGIIHAIETA (SEQ ID NO 327)>orf01969LHINPLNGFIFTIVNMDILSRKGYFFFRKGKDMLLIPVIC (SEQ ID NO 328)>orf01981MTIHIQVVKTNMVILADRLFQGFILRSTDKFFIKIRLVRSHNLRFNSMDFSTVAVHENKGRHHMDELLP RFIINSKATVAKKSIVAQGFRFDGNFFRKTRQTNHLNIIFCDNPDQIIVFQNGLITNSQFNRLHP (SEQ ID NO
329)>orf01988LGHSKAEEHETICSHPFDDHTTETIPNQVKGRDMTSSETLPFPSKNQNQGKAKQNP (SEQ ID NO
330)>orf01991LLLSCRKVIVCFIFSSTWNKNFFNLAFSWNFDNCIRGFFSINSNLFG匪TSLWINIVGPCRGYIAILSV NCNRIFTTVFCFIFFKTNSRT (SEQ ID NO 331)>orf01992MVKRRIRRGTREPEKVVVPEQSSIPSYPVSVTSNQGTDVAVEPAKAVAPTTGWKQENGMWYFYNTDGSM ATGWVQVNGSffYYLNSNGSMKVNQWFQVGGKffYYVNTSGELAVNTSIDGYRVNDNGEffVR (SEQ ID NO 332)>orf02006MRFIVGRFTSFSLGIEFSPTSKLDDLLFKIAFLMILATWIKARKTKGAT (SEQ ID NO 333)>orf02010MANDNKSHYLIYRVLGISFEEGENIDLYQNKGRFLYKYAGSFLEEAAVLSFNEKFGTENT(SEQ ID NO 334)>orf02019LVNCKPLEAYRQLEEAELVGCWVHVRRKFFEATPKQADKSSLGAKGLAYCDQLFALERDWETLSADER LQKRQEELQPLMEDFFAWCRRQSVLSGSKLGRAIEYSLKYEETFKTILKDGHLVLSNNLAERAIKSLVMGRSKRVQ WTLLA (SEQ ID NO 335)>orf02022MFPVETEEITYKRKKSKGKCQALLAQFDSEEVHHQVEESICSDCQ⑶LKEIGATLQRQELVFIPAQLKR IDHIQHAYKCQACSDKNPSDKIVKAPIPKAPL (SEQ ID NO 336)[1137]>orf02023LKIIQQQSATIDSLTNELALLREQVAYLTQKLYGKSSEKSVCPSGQLNLFEEESPSEEDGDVPS (SEQ ID NO 337)>orf02024 LTIPVKDFKAVFTSTTKEKDLTGERIQFKVGFNQISQ (SEQ ID NO 338)>orf02037LVCQTIKYWHKFHLHIGRCKLLIGLIPVLNFFIRADIDCLLVLLSLIDRQNGKQFNLCQWIIASNGLND SFEIIESLIHRNILSDIICPNQKKNFIYCSTI (SEQ ID NO :339)>orf02042MIFSCSDSCFSIILLDGDIHENTTFSPLSILFISHRFNSLIGNEVPH (SEQ ID NO 340)>orf02043MPSKDNIRSPIDHLVIKSFLFFSWFQSILNTHLRHDNGDICFLLCPFNFSLHLIFV (SEQ ID NO 341)>orf02045MVSSKSPIAKSACLVHLLEPRSHILKIFMKVIGTVFFFS (SEQ ID NO 342)>orf02047VVEQIPVGHNSGSFFLFLLLRLLLSPLLRNSISFLTSQGIPffKLSNNKTKPIDKPTASKSIATNPLLLH LR (SEQ ID NO 343)>orf02054MSCTKIGVPFKKLTKKACKGYKILTRLSSQWQKEAPNQSRSAAIXXHSIH (SEQ ID NO 344)>orf02075MNQIQIQIIQAQFFYRFFQSLTSLLIGLLTIPKLGSYEHFFTWNSAIFDCLTNTFFILINRRRIWTIT SLQGF (SEQ ID NO 345)>orf02080MLLLISLTQLIIFLFFERFNLLLKTFLLVDLKSNKSA (SEQ ID NO 346)>orf02095LIFIEYKIADKTITIIGLSRVNVGRRIALLIAYFIAK (SEQ ID NO 347)>orf02098VIPRYVTKHQGWDHNPHTITNSDDDPATLVTFRTFKFNVGNCTIPKNDQNGSSQKFSGILQCPCEIHLL DSP (SEQ ID NO 348)>orf02100VVPKTATSTETKTITRII HYVDKVTNQNVKEDVVQPVTLSRTKTENKVTGVVTYGEff TTGNWDEVISGK IDKYKDPDIPTVESQEVTSDSSDKEITVRYDRLSTPDKPTPEKPEIPSPQEPGTPGEPTPEKPIPQPNPEHPSVPTP NPELPNQETPTPDKPTPEPGTPKTETPVNPDPEVPTYETGKREELPNTGTEANATLASAGIMTLLAGLGLGFFKKKE DEK (SEQ ID NO 349)>orf02105MAYSTDFKQRALDSIKEGHSHVEAAKFFGVGVRTLFTWEKKDVNKDT (SEQ ID NO 350)>orf02143MPILQAKIDSFRPLFDGLTSRFKVGAGLFLKRFSFSRVKQILLALPQFSMMNPIVNG (SEQ ID NO 351)>orf02158MAVQANWSFDITHDSSFFFSNQKRGLNFSQMCFKDRRRNGFFDRKIFKFKFNNPIQIF(SEQ ID NO:
352)>orf02160LFLQIKGIKPNHTIALASYIEQSFFFINKTVHFKIGKQLIRTLQTNPFVIQLNCHLFQGCKKKCSQALS LMVRLDD (SEQ ID NO 353)>orf02168MEIVLVSFSISFQHFIIAYCLDFSSAGFRNSQNFSNFC (SEQ ID NO 354) >orf02180LNFNHVYFGYDENRPVLKDITCSIFKGQKIAFVGPSGSGKSTIVRLLERFYKPLSGDILMEQSSIYDFN LKEWRSKIAWVSQNNAVLSGSIRDNLCLGLNRLVTDDELMKVLDLVSLGDEIRSMKEGLDTEVGERGRFLSGGQSQR LQIARTYLKDAEILIFDEATANLDADSEYAIISSLYSVLKEKTVVIIAHSLSTVKDVDCIFFLEEGKITGSGTHKEL LENHERYARFVQEQMIE(SEQ ID NO : 355)>orf02181LIYAEKSFFDKSQSGELT SAIVNDMSVIREFLITTFPN11LSLVMVLGSIVVLFSLDffNLSLLLFITL PCMMFIILPLSNISEKYSRRLQKEIGFLTGQLTEKIQEHELIKTNQAEKSVQNVLDNCIERVQNNSLKSDRVTSFE TPFALLFIFATIAVMLTYGSYRVSAGYISVGTLVSFLIYLFQLLNPISNIANFVTVYSRSKGS (SEQ ID NO 356)>orf02183MKLKLLRVDTKVIMGSFFLVLSSLLALLLPLILKGLIDGSSIENIGSKVFQSFLIFIGQALFSSIGYYL FSQSGEKKIAKIRKKVI (SEQ ID NO 357)>orf02196LIRYLDQYEDVILREIKAQFPDVAVDKLMEEYIKAGLILRENKRYYLNFPTLESLDSLELDQEIFVREA SPVYQALLEQSFETELRNQINAAILVEKTDFARIKMTLSNYFYKVKQQYPLTEKQQELYDILGDVNPEYALKYMTAF LLKFLKKDHLMQKCRDIFVDSLVVLGYIVQNEDRKYELAIDFDKERLTFYLA (SEQ ID NO 358)>orf02197MIGLKEVCRFLTDNTSLSTSMINHPIQINGNMAIVTCGSLDGLSHV (SEQ ID NO 359)>orf02206MLINDLTFFIFDISPIQSYKKVRLEITNLffNNTKNATSRGDSC (SEQ ID NO 360)>orf02208MRERVRLSGSLFTSLKTREHIKSTMELFHKYVFFLIQEIKIKMINFLKIGDLPTL (SEQ ID NO: 361)>orf02219MIDHFEIKVKDLQISEGFYRSFLAPLDYKLTFKTSSLISFLSPNSPHPGGDFWLTQGTQDPVHFAFLAE NKEEVQACYEAGLEAGGRDNGVPGYRSEHPIYYAAFMIDLDGNNIEVVCHKE (SEQ ID NO 362)>orf02221VIVFLSRNKDGNAFCHLDLISIANPVWGWDDDFITffIDHSHKEGIERIFGSRSDCHLI(SEQ ID NO: 363)[1191]>orf02224LSNQFYFSLQTKPILKVKQFLLFQSQMTRVSEILQFSNKL (SEQ ID NO 364)>orf02227LFRLGQLISLNVAVHKPIKKFQGWIVLSSLPFQSLDILKFFRRFLSRYLVETLQLTGRIESQGIKHGLT FffF (SEQ ID NO 365)>orf02229MEDKEMGFYLMVASMLLGLLALKIGFSQFKEKKDKFLSILTSLAGTALVLVAVffLGffPK(SEQ ID NO 366) [1197]>orf02250MLDSDIGCSRKNLLGLFWIRRRRNIHIVDRAMEKGISNRAPNKISLKACFFNFF (SEQ ID NO: 367)>orf02278LLHPFTRNITCDRHILTLLGNLVNFIHIDNATLCTFDVKVSNLQEFEEDIFHVLTHITSLRQSCRIRNS KRYIQALSQGLGKESFP (SEQ ID NO 368)>orf02279VEIDAFVVVINRHCQGTLGTILTNYIVVQDMEEFNWFWHLRQVCQDFLNQFFSNDFLSQLHAFITNKSI VASNYFLYFFLVFATK (SEQ ID NO 369)>orf02285MNXXGKGEEGEDLVVGVFKWLYSERLRFDTERVGGGGKGK (SEQ ID NO 370)>orf02291MHKNFVVVVTNFFTAVQFIQFNKEGTTCHNTTKFFNHLDSCLNSSTCRQKVIYNKNTLTffLNGIRVHS QGIDTVLFFIVSRNNFAWQFTWLTNRRKTNSQLKGNWTTHDKSTSFRSHDHVDFLVSSILNDFTNSVAISISISHQ RTNITEGNAFLffIIFNCCNVIF (SEQ ID NO 371)>orf02299MLNRQVCFCFVNHISPLNVVIWENLSLEELLYAICICFITHKIAKQTSLTIDNAGIAMNNIR (SEQ ID NO 372)>orf02304LDSRFFCTDFFKGRQAKGCSFSCTSLSLTDNILAFKGQRNSLFLDRTSFYKTSFFNFC(SEQ ID NO: 373)>orf02315LLRKQEREYLRAENAILKKLRELRLKEEKEKEERQKLFKN (SEQ ID NO 374)>orf02320MRFLADQDRIQHHRYSWALFDKVQGLLSHTDSREKTNLNSPKFHITQAI (SEQ ID NO 375)>orf02321MLKNGIISWKDFKSFFCQGCQTSHCYKPMQVVQGIGSQISRQSTTTKNIISRKC (SEQ ID NO: 376)>orf02324VTAHRIFGTSSIHSKLIGLAMLGITAMKIICHKLNRNHINIFRRLGIQGKTEFLLIHLIRQVKMNDLSQ GMNPTICPTSTVNSNDLPFI (SEQ ID NO 377)[1219]>orf02328MLARSKNCFMKSLSIFLLIFYFFDSYQISKKRRSLIGL (SEQ ID NO 378)>orf02339LEVCIHHHHQISCRILQACIKGCFFAKISRERNIMDCRILLPIGL (SEQ ID NO 379)>orf02345LTGNVICHPKLPDKISVKCLYSSKIQFKPRQRRLAMGMVTDFVSSIHNLKAAL(SEQ ID NO 380)>orf02356 MGRKPKKRPEERTELERLQAENEYLRAENAILKKLRELRLKEEKEKEERQKLFKN (SEQ ID NO: 381)>orf02360MDEIKNFRQWGSKTPGHPEVTHTSGVDATSGPLGQGISTAVGFAQAERFLAAKYNKDGFP IFDHYTYVIA ⑶⑶ FMEGVSAEAASYAGHQALDKLIVLYDSNDICLDGETKDTFSENVRARYDAYGWHTVLVEDGTD LAAISTAIETAKFSGKPSLIEVKTVIGYGSPNKSGTNAVHGAPLGAEETGATRKFLGWDYDPFEVPEEVYSDFKTNV ADRGQEAYDAWASLVSDYKVAYPEVASEIDAIVAGKSPVTITEKDFPVYENGFSQATRNSSQDAINTAAVLPTFLGG SADLAHS匪TYIKADGLQDKYNPLNRNIQFGVREFVMGTILNGMALHGGLRVYGGTFFVFSDYVKAAIRLSAIQELP VTYVFTHDSIAVGEDGPTHEPVEHLAGLRSMPNLTVIRPADARETQATWHHALTSTTTPTVIVLTRQNLVVEEGTDF GKVAKGAYVVYDTPGFDTIIIATGSEVNLAIKAAKELVLQGGKVRVVSMPSTELFDAQDATYKEDILPSKTRRRVAI EMAATQSWYKYVGLDGAVIGIDIFGASAPAQTVIDNYGFTVENIVAQVKSL (SEQ ID NO 382)>orf02362LNFLNEPRRQGNIGNKMAIHNIDMIRCYFIIQKSNLLFEFVQIHGHQRff (SEQ ID NO 383)>orf02367VIYSYDYPRLLHSRTLAMGNSNIIPNTGLSFCLSLIKTFDKLVSIRHITRLNQ (SEQ ID NO: 384)>orf02371VSRKQEQMETLLLLLRDSKDYISAKVLGEKLNCSDKTVYRLVKGINKDCPVEAFILSEKGRGFKLNPRS SLVDVDGNFTEAFDPEVRREKLLERLLLTAPKPHSIYDLGEEFYVSESVVLKDRQILQESLAIYGLDLKMRQRKLFI D⑶EAQIRSAILNLLPMFNQLDLEQITQNKVQPLDGELAHFCLGLLITLERELGVNIPYPYNINIFSHLYIFISRNR RSTSIHVVAPSKPTIVDEKIYSVCQKIIQEIEQYFRMKVDAVEIDYLYQYVVSSRLQKPFSSGKLPFSQRVLDVTHY YFSRMCMDNREIETTDPDFVDLASHISPLLRRLDNRVQIKNSLLSQILLTYPNLVKELTTISKEVSLVFGFASLSLD EIGFLVLYFARFQEKRARPLKTVVMCTSGVGTSELLRARLEKQFSELDIIDVVAYHQLDELINLYPDLDFIVTTVAL QEPASVPFVLVSAFLTE⑶KQRLQAKIQEINYE (SEQ ID NO 385)>orf02390MMSMVDPIDQTFIVNLKIRKSQVFSQLQFSCHIVVYPSEVHIYQALVIKLQNHILGPQVLP (SEQ ID NO 386)>orf02391LANRTRIDNQLPTSPVTKQLLVNMSINSNITGRMSHQAVKLLLFASMNQLSPPVLIRQMMANSHRQIPK LTMNLKRLIVEHFNFF (SEQ ID NO 387)>orf02395MDSIEFFHDKTFLFYLTSFYSKRMGVTTKMIKIAEGRFS (SEQ ID NO 388)>orf02406[1241 ] LTRFEEIFEEYKNPQDTFFYPLVYKENTYKKTAISIFALLMLGVCCLFLFSQQSYKKLVQYYANDQNLP SRITYSEYSDK (SEQ ID NO 389)>orf02414MIAEFIDGLQKFHFLQNALITAIVVGIVAGAVGCFIILRGMSLMGDAISHAVLPGVALSFILGLDFFIG AIVFGLLAAIIITYIKGNSIIKSDTAIGITFSSFLALGIILIGVAKSSTDLFHILFGNILAVQDTDMFITMGVGAAI LLLIWIFFKQLLITSFDELLAKAMGMPVNFYHYLLMVLLTLVSVTAMQSVGTILIVAMLITPAATAYLYANSLKSMI FLSSTFGATASVLGLFIGYSFNVAAGSSIVLTAASFFLISFFIAPKQRYLKLKNKHLLK (SEQ ID NO 390)>orf02424 LNQEIIWKTRKSFTFKSRSLTDIRSRRKCLTNIQLSLIVRHLRQSRTLLAELNVNIPKRQIGPILTRFW PN (SEQ ID NO 391)>orf02437MQGEMRFSLVQFLTTLIKFCIFPFLLPNWLFGRKACTHWEFSFPKIKGVFEFHGISFINNNKLKTTTSK KDENRGTTFIRKKI (SEQ ID NO 392)>orf02438MYEEPEVAPVHPTGPTPATETVDSIPGFEAPQESVTIL (SEQ ID NO 393)>orf02468MRLSWHFMRFKKLPLLINQTILDVGSTDINCNVICHKYLLLD (SEQ ID NO 394)>orf02470MGNNGQFTFGYRHDFFQNQLAIFNALVDTFTRRTIDIKTLNTFINEVLNQGTRTFWAYFSLIIITCVEG WNDTFVFFQI (SEQ ID NO 395)>orf02497LSTRNKYCKNLIIFESTFNILDIVKKDLKLNSKLEKDLKY (SEQ ID NO 396)>orf02499MNRSVQERKCRYSIRKLSVGAVSMIVGAVVFGTSPVLAQEGASEQPLANETQLSGESSTLTDTEKSQPS SETELSGNKQEQERKDKQEEKIPRDYYARDLENVETVIEKEDVETNASNGQRVDLSSELDKLKKLENATVHMEFKPD AKAPAFYNLFSVSSATKKDEYFTMAVYNNTATLEGRGSDGKQFYNNYNDAPLKVKPGQWNSVTFTVEKPTAELPKGR VRLYVNGVLSRTSLRSGNFIKDMPDVTHVQIGATKRANNTVWGSNLQIRNLTVYNRALTPEEVQKRSQLFKRSDLEK KLPEGAALTEKTDIFESGRNGKPNKDGIKSYRIPALLKTDKGTLIAGADERRLHSSDWGDIGMVIRRSEDNGKTWGD RVTITNLRDNPKASDPSIGSPVNIDMVLVQDPETKRIFSIYDMFPEGKGIFGMSSQKEEAYKKIDGKTYQILYREGE KGAYTIRENGTVYTPDGKATDYRVVVDPVKPAYSDKGDLYKGNQLLGNIYFTTNKTSPFRIAKDSYLWMSYSDDDGK TWSAPQDITPMVKADWMKFLGVGPGTGIVLRNGPHKGRILIPVYTTNNVSHLNGSQSSRIIYSDDHGKTWHAGEAVN DNRQVDGQKIHSSTMNNRRAQNTESTWQLNNGDVKLFMRGLTCDLQVATSKDGGVTWEKDIKRYPQVKDVYVQMSA IHTMHEGKEYIILSNAGGPKRENGMVHLARVEENGELTffLKHNPIQKGEFAYNSLQELGNGEYGILYEHTEKGQNAY TLSFRKFNWDFLSKDLISPTEAKVKRTREMGKGVIGLEFDSEVLVNKAPTLQLANGKTARFMTQYDTKTLLFTVDSE DMGQKVTGLAEGAIESMHNLPVSVAGTKLSNGMNGSEAAVHEVPEYTGPLGTSGEEPAPTVEKPEYTGPLGTSGEEP APTVEKPEYTGPLGTAGEEAAPTVEKPEFTGGVNGTEPAVHEIAEYKGSDSLVTLTTKEDYTYKAPLAQQALPETGN KESDLLASLGLTAFFLGLFTLGKKREQ(SEQ ID NO : 397)>orf02501VDRTDEVSSKHCFEVVDRTDEVSSKHRFEVADRTDEVSNIYTARQS (SEQ ID NO 398)[1260]>orf02512[1261]MSCNCAFYRSQFFDVNSVSNYHSHQKELRFPNSILFTYFVKVT (SEQ ID NO 399)>orf02535VGLIKLTSYVFVCISNSFLTRHDKNDNICFFHGNFCLVLDLFHERSIDIINSSCINHAKRTIEPLTRCI NTVTCHSFDIFYNGDSLTSDPIK (SEQ ID NO 400)>orf02537LSSKSCIDRTNQETFHTLGLEGVGMKSGSLFCSVQISDKEKENSRLANGFLRYQFIQGIFLLLTSYHNH RVGLEILPR (SEQ ID NO 401)>orf02554MKSKEQTRKLAVGCSKYSFEVADKTDEVSSKHCFEVVDRTDEVSNYIYGKAKLTWFEEIFEEY (SEQ ID NO 402)>orf02556LSNSFFLIKFSSSKISGKKRIVSDNIFIRNKFICHFKKE (SEQ ID NO 403)>orf02564MDYSKVAAEVIEAVGKDNLVAAAHCATRLRLVLKDEAKVNQAALDNNADVKGTFSTNGQYQIIIGPGDV NFVYAEIIKKTGLKEVSTDDLKEIANKDKKFNPLMDLIKLLSDIFVPIIPALVAGGLLMALRNFLTSPDLFGPQSIE DMYPAIKGFSAMIQLMSAAPFMFLPVLVGISAAKRFGANQFLGAAIGMIMTTPDLGGKEAFWDILGFHVTQTNYAYQ VIPVLVAVWLLANLEKFFHKKLPSAVDFTFTPLLSVMITGFLTFTVIGPVMLVVSDAITNAIVWLYNTTGAFGMGLF GGTYSLIVMTGLHQSFPAIETQLLSAYNNNGTGF⑶YIFVVASMANVAQGAATLAVYFLTKNAKTKGLSSSAAVSAF LGITEPALFGVNLKYKFPFFCALAGSAIGAFVAGLTHVIAVSLGAAGFIGFLSIKAGSIPMYIIAEIMSFVAAFAFT YFYGKTKAASVFADEAATATAETVTEPTVEAPVVEETDTLQNETLVTPIVGDVVALADVNDPVFSSGAMGQGIAVKP SQGWYAPADAEVSIAFPTGHAFGLKTRNGAEVLIHVGIDTVSMNGDGFEAKVAQGNKVKA⑶VLGTFDSNKIAAAG LDDTTMVIVTNTADYASVAPVATGSVAKGNAVIEVKI (SEQ ID NO 404)>orf02570MTESYTWVEADRATLSRYRHGQGHLTDQFFSFKVQRPAAKTLIASISTGKGMGPSFDGTPVITSGNQ NRINTIKNSFIMSSSSVRISLRKLTSQRNFLRNLSSLILLAAQVAKGDATACSHQRIGRVVGQDSHETLSLTEFF (SEQ ID NO 405)>orf02571MNlNNEKVffFAFYLLDMQITRPTSTFNDRRIGLIGKLQELRFLAGNLLLR (SEQ ID NO 406)>orf02572LIKGYLPNHLSLMDLCSKTTCTLDDFAGIAGRRNHRGFFCHIGNGVFLTVDKYLWNQ(SEQ ID NO: 407)>orf02578LIKLTGRNFSDILIKCLVKCFTNLLSNQLMLLPSTLKL (SEQ ID NO 408)>orf02582MIQSENHCSASHSNRDYQSQHDNQGRTCQCFIIVPCHKKGSCSVGEITWNQRCQNGQDKDHSRCLIKNT (SEQ ID NO 409)>orf02589miarqlmvffstnqadtri msidsliinnskdfqssshasvsfiltklvnllifnf(seq ID NO:410)>orf02590MGEPFTHFIDCIDLGINPSYTQVCHRHFTSDIPCAMTSHPIS (SEQ ID NO 411)>orf02597 LSSDSHFIGIKAFVILILGKSNSIVLRIVGLYQDLTCLFSTTCSTCHLSQELEGSLRRTEIRQIQGRIR I (SEQID NO 412)>orf02598MAVHSLGIHMQGQRNIAVGTSIHRPTLPTHDKARITTAIEHENHLLFFNQTVLDSL(SEQ ID NO:
413)>orf02599MVTGIAVLLISRFMLFINNHDTQIFQRSKDSRSGTNNNLGIATLHLAPFIILFTIG(SEQ ID NO:
414)>orf02600VKNGYLVPKTCYKTLGHLRSQGNLRYQQNSCLALIQGTLDNLQVNLGLPTSCNPLK(SEQ ID NO:
415)>orf02601MVNLIPRLGLDLLLIDCLIFQTKQAFSSQTHHFSLLGKV (SEQ ID NO 416)>orf02602LGLQTKNNPLNQAITLTKRHMNPHPNFQHSLKFLRNPVTIGLVRLHQGHIYDNLS (SEQ ID NO:
417)>orf02605LGNHFCTICSTTYQAFLQFIQIffffCQEDKDSIWNLFLDLKSTLNFNFKENIDSLVQGFIDIGQRSSIVV ADIFCVFQHLSLTNQLFKFFTSTEEIVNTVHFSRTLCACRHRYRILKLVFRTLKNLSSNRSFSNP (SEQ ID NO
418)>orf02618VLLPNVLIKFINRFCWNVIPIKGCDSTFWNNKLIAIFKGNLDRGIHTIFCLHTT (SEQ ID NO:
419)>orf02628VGCSYICHELVTNHDHFLFVIVEFLHSTVNTKCEGLQGPVNVINPKFLNCSLNAFFGVI(SEQ ID NO 420)>orf02629LLHLWRSIRVVPSNEGIIQIDQNSLDSLRLQAGDCQIIDCFHSKIffYIIFNRHSGSFS(SEQID NO 421)>orf02631LFGSCRQINHTSLQIRQGKEVFLGSSLAQEVIDLIPTLVHLLNDRIVGIADDFQTGKEKLINRKRVMAL QITSHLFNDIGVLGITNGNQATMLDNKGHGKSLIVGXXHSIH (SEQ ID NO 422)>orf02633VKGLLLATKLCRTNSHTDNLTRYSNRSICQNDLISHIQLTFKEDEKAIDDIRQKALGSHTNRYPSNTSS SQQTRNWQT (SEQ ID NO 423)[1310]>orf02635LWGILGLTLPNLSGIGLL ⑶ LFVGGLKAVAPILVFALVANALSQHQKGQDSNMKTWFLYIL (SEQ ID NO 424)>orf02637MIGTFAAALVAVLASFIVPIEITLNSANTEIAPPDGIGQVLSNLLLKLVDNPVNALLTANYIRILSffAV IFGIAMREASKNSKELLKTIADVTSKIVEWIINLAPFGILGLVFKTISDKGVGSLANYGILLVLLVTTMLFVAPVVN PLIAFFFMRRNPYPLVWNCLRVSGVTAFFTRSSTTNIPVNMKLCHDLGLNPDTYSVSIPLGSTINMAGVAITINLLT LVTVNTLGIPVDFATAFVLSVVAAISACGASGGASGIAGGSLLLIPVAGSLFGISNDIAIQIVGVGFVIGVIQDSCE TALNSSTDVLFTAVAEYAATRKKASLLMSCLLRFYSNLLGNSYVY (SEQ ID NO 425)>orf02639 MIAHAIIILLFKNAGKLCFLVVFFFTVHTFGKNQLLLG (SEQ ID NO 426)>orf02645VFEVVDKTDEVSSKHCFEVADRTDEVSNHTYGKVKLTWFEEIFEEYHTKKPCSSR (SEQ ID NO: 427)>orf02651MKNRIIDVFEVVNRILVITVENPDFEDLRVNQFVKIGDKKYRVRSGPMIHSTPPQSVLDRDTFTIDYTD DELLDKEAVFTTH (SEQ ID NO 428)>orf02657MAYIEYKQRGKKRLWSFSIRERSKSLLHKSGFKTKREAKIEAEKVLHKLNTGSVLSSSMTLSELYNEWL DLKILPSNRSVVTKKKYLMRKKVIERLFGNKPVSQIKPSEYQKIMNEYGETVSRNFLGRLNSSIQASIQMAIADKVI IEDFTAYVELFSSKSGQKVEEKYLHTESDYQKVLVYLKNKFDYQKSIVPYVIYFLFKTGMRFSELIALTWDEVDELN EQLKTYRRYNTAIHKFTPPKNNTSIRLVPITSDMLSLLKTLKILQLKTNKELNIDNENNLIFQHFGYVYDVPDIAT VNKAIKVMLKELQIFPLITTKGARHTYGSYLWHNNIDLGVIAKILGHKDISMLIDVYGHTLEEKISEEFTAVKSLL (SEQ ID NO 429)>orf02658MKDTISNKDLISMGYRPSTANAIIHQVRELLVSRGYTFYNRKRLMVVPKSVVKELLGMEL(SEQ ID NO 430)>orf02659MNKEVLNRAPSNSPITIHQMSNKSYSKFQEEVSLKYGFIGLKLDKLSLTAEVSEEFHSEILSGNFTLYD YFGVVEPNLNRNGELASYKGQFFNDEKENWYIEYTPVASIKMNKRPLKIEFTPSKVSKKNFLIVFHRMFPYMFNIAI STFHLAYDFERDLSALRVNWPKVMYRPIYKGMKLETMDFGAPKGNYHLTAYNKLKERMDSGDMAEIEIYQQYDNLWR IEYKFYNEGNIKKELKNGLPFLAKIPVYIENFKGLEFNNLGVNEKIYLFALRNKPELFAESDKRTVAKYKKLAESIS EVNLNVFFQNALDFVEIFNQEPCLINFFEFMNSMLQ⑶IPKLTINQE (SEQ ID NO 431)>orf02660MHFDKSKFGAVFSAPGLYEVEVINNASFGQNAQYEVIQSRKLGTFAELIEMAKIK (SEQ ID NO: 432)>orf02661MFKIKQTASLSEHYFLNTSKLRSIRWFTIGFLSILSLYSCILFKGWFLQMFTLSVGLIVTLYFERKIK GCFHQIEPLLIVRENLLFMLRRNSFLFTATKDGAILRSAKFNYQLNDVSIVIQALKSGDEFTREMDDLDVLLS SVLGISLSYKEIYATHVEYVFVYRQPERLHITSLPLEEDNSLKIKIYDDFIIDLRKNFSMLISGASGAGKSFFTYYYLTR FISQTVNGRHAKIYVIDPKLSDIYKLSKFSGLPVENYGTTNEDAFRIVRHYINEMNRRMEIYNKSDLFDSIGIDLGL PPLLLVIEEYSSLVASMDSKAKKDFE匪VAIVAQKARSLSMGVCIVMQQPRSDSLSTNIREQLVNAIFLGAPTRES SQMMFGTTDVPKVKKDKGVGLYSTDREPPKEFHSPMFDRDVFEVILPVWEWAAKDYMKDEDEDV (SEQ ID NO 433) [1330] >orf02662 MKQKQPIVSRTKQHTFEELIQDQKLERLANLSPDLVGRYGFTASCASSFANLIKEAYGGKNLNVVYASR MLALWNIACSCYHKADGYSLADALFSDKKICLDYFYYHNNTSDIITLDMIEDVKKNYLQLVTTATSD匪SVIEFEME KESDLYYFIKATLGSSFSRMHYSVLVKALAGALAKNI (SEQ ID NO 434)>orf02664MGWKGTPPCLHPSNQDTTILIVQQCLRRIEVLAMINFLN (SEQ ID NO 435)>orf02665VFGSYYGVIASIFFKEFWITEISSNQLIWQVCSSYNWILGNLFKVNPVI (SEQ ID NO 436)>orf02666VLPSHQVLTFSMSPVHRPPNTIIffIELIKEMVFSTKIDKSIffIIDPTNLS (SEQ ID NO 437)>orf02689LIVSLKTKSRKAKDMAESIQGffLAQFLVNLFKSITFDCGKEFSKffKDISNHHDSESFFANLGCPRQRCL NEHSNRLLRCHDLPKQTDFNEVSQEF (SEQ ID NO 438)>orf02690 VVEIIYFLI11IASGLGSISGMGGGIIIKPLMDSFGYHSVSDIAFYSSFSVFIMAIISTTKRFSQSKEI KWRLIFTVSFSSVLGGFLGHLIFQVLLSQLSVRLVSIVQMILLFVMLLVSFVLTDFKKTYQFDKIGFYMICGLLLGL ISSFLGIGGGPLNVSLLMVFFSISIKEATMYSLAIIFFSQLSHLATIVVVTGLNQYHLAPVPVIFLASICGGVLGTV VSKVLPENWVRYCFKGMLFFVMGMTLYNLFHIL (SEQ ID NO 439)>orf02691MMGTNSEEGFLDDFEGPQVAVSVKDFSIADTPVTNQEFAQFVKETGYKTLAERQEWSFVFILFVPEAER EGYPHPAGAPffffLQVSNACWKHPYGENSNLVGLEDHPVVHVALEDALAFCNWSGMSLPTEAQWEYAARGGRQSEYPff GDTLLEGGYYHANTWQGRFPYENTALDGFIGTAPVYEFLPNDFGLYQMIGNVWEWCRNPRYTLLASFNEDDYELPKY GIQDEEYAIRGGSFLCHCSYCNRYRVAARNGCISTSTSSHLGFRCLKE (SEQ ID NO 440)>orf02694MVQTKQPNIILIVVDQMRADALSLNSKDKLVSTPTLDMMASVGYNFENAYSPVPSCVPARAALLTGLDQ DKSGRVGYQDEVPWNFTNTLPKVFKDMGYQTECIGKMHVFPSRQRLGFDHVLLHDGYLHVDRKYDKTYGSQFDYASD YLAFLKGKVGYDVDLIDDGMDCNSWEARPWDKDEKLHPTNWVVSESISFLQRRDPTVPFFLKMSFEKPHAPLNPPKY YFDMYMERLPQFLDLHIGNWEVLEKQIPSIYALRGKLKEDDQRRMVAAYFGLITHIDHQISRFLTALKEFRHDKDTI IWFVSDHGDQLGEHYLFRKGYPYQGSIHIPSFIYDPAGLIAGNRGTIKQLVKIQDIFPSLVDLAGGTTTDELDGRSV KNLLFGQYEGWRTEFHGEHALGKDSSQYILTDQWKFIWFPVLNHYQLFDMKKDPHEMNDLYPSEKYQPIVRQMKKKL VDFLRYREEGFWDEELVPVELSKITPTLTKTCDSQS (SEQ ID NO 441)>orf02696MNTMLDKMQEKLSPIAMKVGNQKFLVALRDSFVGTMPVIMTGSIALLLNAFLVDLPQQFHLESITKTF QWLVDINNLVFKGSIPIVSLLFIYCLGVNIAKIYKVDTVSAGLVSLASFVISIGSTVTKSFPLANV⑶VKLDQILQGIDNLAFDGKNLMVTIGNVIPGNHINARGYFTAMMIGFLASIIFCKVMKKNWVIKLPDSVPPAIAKPFTSIIPGFMA MYIVAILTYVFHLLSNDLLIDWVYKVLQTPLLGLSQSFFAVILMIFLNKLFWFFGLHGGNVLAPIMEGLFGVAMLAN LDAFQKGEPIPYIWTSGSFGAFVWFGGLGLVLAILIFSRNSHYRKVAKLGLAPVLFNIGEPVNYGLPWLNPLLFI PFVLSPVFMATVAYWATSWGLVSPVTQNVTffVMPPILYGFFSTAFDffRAIILSVVCLIISVLTYFPFVKMADKTELS (SEQ ID NO 442)>orf02697MDESNLESVMGLIMYGGEAKSNAMEAIQAAKK⑶FSKANRRLADANAALLQAHKAQTEMLTREAQGEET SISLLMVHAQDHLMTSLTFVDLAKEVVEVYERFEKN (SEQ ID NO 443)>orf02698 MAKVTIMLACAAGMSTSLLVTKMQKAAEDKGLDAEIFAVPAPEAEEIVATKEVNVLLLGPQVRYLLCiDF QEKLKDRQIPVAVIPMTDYGMMNGSKVLDLAESLLD (SEQ ID NO 444) >orf02699MKRLISANPSEILQMNAEELKQSI LASEGRVVLSENWTRETFViiD ITNSEIARAFGADMILLNCVDV FEPKIYALDSSGDDVIHRLHQLVACPIGVNLEPIDPSAKMLEETQEIVAGRVASVETLKRIEELGFDFVCLTGNPG TGVSNREIIKAVQTAKENFSGLIIAGKMHGAGVNEPVAELSVAEQLLEAGADVILVPAVGTVPAFHDQELREVVD LVHSKGGLVLSAIGTSQETSDTDTIKEIALRNKICGVDIQHIGDAGYGGLATVDNIYALSKAIRGVRHTVSRLAR SVNR(SEQ ID NO 445)>orf02700MEKLLQEKLLPVAARLGNNKALVSIRDGITLTIPLLLIGSLLMVIASFPIPGWEKYL⑶IGVADYLWKG VDSSFGLLGLVASFGIAYFMARQYKVDGIPAGIVSLSSFITVTPFITGEAGAGMPTAFMASKGLFVAMILGLINGYI YQWFINHNIQIKMPDGVPPAVSKSFSAIIPGAVTIVGWLIVYATLDKLSLPNLHEIAQVALGGPLGLLGNNVIGLLI LIFLNSSFWFVGLHGGNVVNAVMKPLWLANLDANKVAYQTGETLPNIFTSVFMDNFVFIGGGGATIGLVLALGYLAH KKKASKQLKTLAPITVIPGLFNINEPAMFGVPIVLNILLLVPFILAPMFNLLVAWGAMASGLVPLTYTDPGWTMPPV ISGLLATGSISGSLLQIVLIVLDVLLYLPFVIAIEKRFKLLED(SEQ ID NO :446)>orf02701MTLSKKQLQLRAKILETVYTLGPISRIEIATKTGITPATTSSITNDLIKENILLELGEDEHDTSVGRKK ILLDIQAKRFYYIGCELSEKHFTFAL⑶NLGNILKEEKEIVTKQLIQEKGNQLINQTLKQFLNNCSDYEIEAIGIAL PGRYLDDYKITTNNPLWQHIDLEMIQSHFDKPLFFSNNVNCMAIGKRLFSRQQNDTNFAYFHFARGMHCSYIYDGNI YGKGNLMIGEIGHTVVSSEGEECSCGRKGCLQTFAGEAWLIKKSKILYHQSPYSLLPSLVKNADDIDIQVILTAYQL GDTGIITLIHQALLYLSQTILNISMMIDSQKIYLHSPLLTNQHIIQKLYSEMNYKPKLLYNRLPEVIIEPYNDFTAA HSAIALCLYHTILHS (SEQ ID NO 447)>orf02719MPFKENLICQHRNHHCSVFFISLGLLHNIHIEIDISQTRASFLDLSDYLQAVLMILQKFCQAIGLAQRL DLLQLHLLHLTRLLL (SEQ ID NO 448)>orf02728MYLLLLVVKDHIALIDKEMHVWRPNCILRDLTNFFIKRNHIVTNKTNGSPTKREV (SEQ ID NO: 449)>orf02729MVLALMNHFIKEIQGIPINRLTILIENSIFKLNLKNWIIG (SEQ ID NO 450)[1364]>orf02731MKIKEQTRKLAAGCSKHCFEVVDRTDEVSSKHCFEVADRTDEVSSKHCFEVADRTDEVSNHTYGKATLT RFEEIFEEYKGVPR (SEQ ID NO 451)>orf02743LVEQLTFNQWVTGSSPVRVIYAGLAELADAPDLGSGA (SEQ ID NO 452)>orf02745 VCQRMDARTCKTTIIAVHNVLTALQQTffIAVQLYQTK (SEQ ID NO 453)>orf02746LHLGKSILSLPVKGKDLEFLVHLFVINHWIGFPSRTSTFCRCKVLNGME (SEQ ID NO 454)>orf02747LEQTVIIANNPCELYWDNHLSFLSDSLLKQVIVHLKRICLDIHHDRGCSHVRNDTT (SEQ ID NO 455)>orf02749LTDDGVLILVVDAGWRGNSCLQEQGCHHFRAILLCITWHFRSCTDKGHLTFKDIDQLRQFVQTDTSDEI SNLGNTAIVSRSHQTSFFIRIRHHGTKLPNLEPTVVLGHTLLLVNHWPLAIQLDPNAQDEKDGRGQNQ (SEQ ID NO 456)>orf02750MLKMRKMGEVRTSKIKAKTQSKQRLKISEPFLLETSff (SEQ ID NO 457)>orf02765MDYNAVIPEFLVSNIEQSRSFYCGLLGFRIEYQRPEENFLFLLKSVN (SEQ ID NO 458)>orf02766 MLEEGTKDQLAELTYPFGRGVNLSFGIKDVSKLYQKVMEANYPIYRPLTKRKFRVSDPYIYPHKFAVLD PDGYFLRFSE (SEQ ID NO 459)>orf02771LACDKHGKGCFTDISALLIGDIHIHHTGCTTLMDTFSFNGQYIVEFSCLKWDRGLECHPIKSQRDNHQ TTDLVT (SEQ ID NO 460)>orf02773MGIAIVVERRVHYFGRHHNVTISHFFNFVIFKGRYSVKMKVFHRFLLIFQTTL (SEQ ID NO 461)>orf02784MIACRHDICKSQKGLEHPFCIVRRLTRDFNQRPVCIVEANIFCLKITPQIIAWIVARTVKSSKTGITL TTSMCKRDNHKITWFHRRNGFPSFFNNPNRFVSTIFVSNFRFWITVPP (SEQ ID NO 462)>orf02799MNMNKDQIAILNGADNLNLTLWMTLKEICKEGCKSFFPVRNTCRMLDIGIPYRLGLSLSNSSVLNGMDV (SEQ ID NO 463)>orf02814MDGQLHHRAIFDWVHFENFINSWLGFLTINLKTTGQGAEIVLIGHTFNTRDINLVNLITRVNHLVCKVP IIGQNQDTRCIPVQTTHRVNTFFDIGQEVDNRLATLVICYTGNDTAWFVKQIIDLFFVVDRLTFNFDLVA (SEQ ID NO 464)[1392]>orf02820MHKLRIFVNQLYRRFGIILGPFLVLGFQVLTQELELAIFFDLREEVLLQVIPQVCHFCYLRKEFTTLNQ HELTSHDHVLTRHFQTHGLQG (SEQ ID NO 465)>orf02831 [1395]MLHMNLFFQPFFTNLCKTLATGCCVKTVMEWSSIATTIDFKIIE (SEQ ID NO 466)>orf02832LDNRAKEffIMSTAQNQAIHLSNQGTQGFIDHLLGNTG (SEQ ID NO 467)>orf02843LSNFCFKTVTVHRYSVNTNVNQNFSTISCFQTKSVPCffKGN (SEQ ID NO 468)>orf02853MKIKEQTRKLAAGCSKHCFEVVDETDEVSNHTYGKATLTWFEEIFE (SEQ ID NO 469)>orf02858MSIVKSHSFSISLGIFNSFffNNIHTSECFYFLCKGKSNRSNSTISVNQMVFFINIQRFYCFAIEDFCLL RI (SEQ ID NO 470)>orf02859LNTLLPPDNLCLFTIYLTGFSCICINSYCHNFWEIFNQLFYQLS (SEQ ID NO 471)>orf0286SMIDKVIEQYKSHDNLDIRVELHKKYSKNKLGFNNWIFSNYQITDEVKVLELGCGTGELWKSNSDSIDKM KQLIVTDFSKDMVKSTKSVIGNRNNVNYEIMDIQKISFENETFDIVIASMLLHHVNDIPKALSEVNRVLKTGGIFYC ATFGENGVVNYLASLFKDEVNQDLENRTFTLQNGKRYLSRYFNSVDTLLYDDELQVTSIDDLVKYIQSFKGISEIGS LEEEIIRKRLESEFNNGMLIIPKEYGMFIARKES (SEQ ID NO 472)>orf02867MDLGFDYFGSALTISPHKNSQTINSIGIDVQKIYTPHYLPNDFKKNQGYKRSVEMCEEYDIYRQCYCGC VYAAQAQNIDLV (SEQ ID NO 473)>orf02868LTKYADVTIYFANSNIHPKAEYHKRVYVTKKFVSDFNERTGNTVQYLEAPYEPN (SEQ ID NO:
474)>orf02876MYNKVILIGRLTSTPELHKTNNDKSVARATIAVNRRYKDQNGEREADFVNMVLWGRLAETLASYATKG SLISVDGELRTRRFEKNGQMNYVTEVLVTGFQLLESRAQRAMRENNAGQDLADLVLEEEELPF (SEQ ID NO
475)>orf02880MQFTRTAHHTKTLFTTKFTWENEIPFWHHSSRKRDNGFQPHTRIGSSCNDLYSLITCDCNLADVEWTI WMGYHLNNFTDNKLRFLIINNFFCKTFRLQLLVQTSDLLICQKDLTALCNFK (SEQ ID NO 476)>orf02885MSYSVDDVVSNAFKKRMILDSFFAFNCSGTMKVSTWVYDKGEWYYVSSSGAMIANDWVKDNGK (SEQ ID NO 477)>orf02895LTSFCFKANMFNNCLRICRIAEGHILKLDLTFEVFISQLHLNRVLDRRMQI (SEQ ID NO 478)[1420]>orf02897LINPLSRDHSSGKNDEECSHEKEAHDNLHSIRHENNHVTKERQTRYRSSVVNHIGPNPVNRHTQTT (SEQ ID NO 479)>orf02900LHLRTCFVRQTNKLSPLINRTRLQFHQTILHYTLNQITSNRLGNIEFLLDIFNQDQVLVFLAIIQKMHN LTLRPTHKFNAATFGFLLHHQVNLMTKTLKD (SEQ ID NO 480)>orf02916MLEIWKYRPFVSEFWNDFKNNHDKQFVDPISLYLTLKDDDDPRIEEESEALENMILQYLGEDDAS (SEQ ID NO 481)>orf02918 LTLFFFELLICLLNSEFDLSKFIFVYFDEYFHEDSLKMNLHQFSFSF (SEQ ID NO 482)>orf02924MAFNQFNRCIGLSIPTAPNVPGTIINRSYLHDATVPNNVREKT (SEQ ID NO 483)>orf02940LRLQIELTWFEEIFEEYKFEIMKIRQTGGCFVSHLTERDGLRVT (SEQ ID NO 484)>orf02944MKKNRGIQKLAILVLLGVFMFSNTIPYQQFIQKNRQLEIRVQSQKKSNGLDVGKAD (SEQ ID NO
485)>orf02946MKKLFILISNLLASLFFVWVLTIWTDTYVSHYYPNVVVRDSSPETTFQHVATRLEKLAEETDSFIAIQH QDPNSEGTTVFSYTTF⑶GKLPDGLQEKNLEDAQSSSVETNYFVFDGHLDIHLLREELSQLGLTNMHLTIPSKLSTL MAIFSNGFQLISLLIFILTFVALTLISQISQLRSSGIRLISGEKRWSIFLRPVGEDLKAIAVGFSLAGVLAILMQKI LSLPTQSLMTIGEGLLSYNLILLSISLFFAQLFAVGIKKIHLMQIIKGQVPVRGIISLILIGQLLAIIIVTLGIGSS LKYSQAWQQHRIGQEIWSQERQLITLSISREGTSPGFDEQAQRKLRTWYQLMDLAVSEQKAFLSRHQLIDRTLQNGM ASSKNLITSTEWHDYNPNGNVLIVTPQYLERQNIPVDTTIEQKMNHLNVGEFVLLLPEHLRSEEEHYKSVFEDDLTS RISSQDERQQMTATVGYLESGQDRFVYNTTPISYQQFLKDPIIIVITPQSTGPQSILFffIDAVQNYVLFNQLSDAQE LIQRQGIENWVSEMQTGYHNYITLLDNIQRERWVMLAGAVLGIATSILLFNTMNRLYFEEFRRAIFIKRIAGLRFLE IHRTYLFAQLGVFLLGFVASVFLQVEIGVAFLVLLLFTGLSLLQLHVQMQKENKMSILVLKGG (SEQ ID NO
486)>orf02955VLKWCILRINHHISRKVDNFLEGTRAHIKGQAHTAWNPLEVPDVRYRSFQFDMSHTLTTNFRTRYFNPT AVTNNSSVTNTFVLTTSTFPVFCRTKDHFIKESFTFWFQGTIIDCFRFFDFSIRP (SEQ ID NO 487)>orf02962LVDPLVTSHDNLLSKGSIFIQTRVSLSYSIFIFFISCQPNNFRS (SEQ ID NO 488)>orf02966MPWKELCHKLAPKVFKVIRIYSRENKKSPSNWAFCSFET (SEQID NO 489)>orf02970VSVLFFCSYFSLSLEKGWFSSLISCKFMNQFLPFCWRQDSPWILTLAQDSITYH (SEQ ID NO 490)[1444]>orf02978VTDENTRKVRSLVAFFSIVIGYILSSFFISLYHLWQEALRGLL (SEQ ID NO 491)>orf02979MRLLFFFANRVIRSKENSSTCPSRSYNLLINTSNVSHITIAVNGTCTGNNTTITKIWVSYLSIDS (SEQ ID NO 492)>orf02983VDSLFLSLGEEGNQEINLQESFSSTDCNPTLISPETTVAQGLCQDIIYRPFT (SEQ ID NO 493)>orf02985VNPKSLGSFFLQDSKGFKELVLGHAKLSLPRIVHNVCPQFKNASRIITTRDDFWNACYSLQMFNIFKG IQVNGRTQFTCIGVFLVWRVVGREHNLRTQKVQFMAHQKLYITRAVHTTTFFLENFQNSWSWSSLNCKIFLKALVP RKSLVDGSCLLTNPLLIIQVKGSRELGNNRF (SEQ ID NO 494)>orf02989MTTIRSLLLNFISISYSIFIQKIKKQTRKLVAGGSKHCF (SEQ ID NO 495)>orf03003MDALVLQKNQETIQQIAVKIRFLDGHDYYSLIDIDNRRTNQTVFPFVNFEDIAF (SEQ ID NO 496)>orf03004MAFFTEIPTRACLINLAITLHIVETCQGFNDLSLHLRVLAL (SEQ ID NO 497)>orf03008MLLPLPFNTSKIKQIAMHSDLNQKEMIGHIFHDEDIF (SEQ ID NO 498)>orf03013MKQTVKKLALVASIAATLGGSVAVASAAVQYPEGGVWTYGSGNGGAYSNYYHPSKYHSSTVVSRKTGSS DKGYAGAGGTSRAffIRTSffGEKVAFYYNV (SEQ ID NO 499)>orf03018MLNRRFIKTNNIHLCHTHLSSQGNFFCLTTCKFFYIQVCMCIKNHLF (SEQ ID NO 500)>orf03029MNTIERTRRLVKGCATHCFEVVDRTDEVSSKHCFEVADETDEVSSKHCFEVADETDEVSSKHVFEVVDE TDEVSSKHVFEVVDETDEVSSKHVFEVVDETDEVSNHTYGKATLTWFAEIFEEY (SEQ ID NO 501)>orf03033MLERLKSIHYMFWASLIFMLFPILPVVIGELPAWHLLVDILFVVTYLGVLITKNQRLSffLFffGLMLVYV AGNTAFVAGNYIWFFFFLSNLLIYHFGVRSLKSLHVWTFLLAQVLVVGRLLIFQRIEVEFLVYMLVILTFVDLMTLG SVRIRLVEDLKEAQVEQNTQINLLLAENERNRIGQDLHDSLGHTFAMLSVKTDLALQLFQMQAYPQVEKELREIQQI SKESMCEVRTIVENLKSRTLTSELETVKKMLEIAGIEVETDNQLDTASLTQELDSMASMILLELVTNIIKHAKASKA YLKLERTEKELILTVSDDGCGFAFLKGDELHTVRDRVFPFSGEVSVISQKHPTEVQVRLPYKERN (SEQ ID NO 502)>orf03036MTWKVEKLSKKIKDKEILRNISFEINDGECVALIGPNGAGKTTLLDCLL ⑶ KLVTSGQVSIQGLPVTS SKLDYTRAYLPQENVIVQKLKVKELIAFFQRIYPNPLSNQEIDQLLQFVKQQKEQLAEKLSGGQKRLFSFVLTLIGR PKIVFLDEPTASMDTSTRQRFWEIVQELKAQGVTILYSSHYIEEVEHTADRILLLNKGELIRDTTPLAMRSEEIEKHFILPIAYKEWEQSNLVENWTLKQDSLQWTREADAFWELLAQAGCRMQEIEVNNRSLLNTIFEETQK ⑶ N (SEQ ID NO 503)[1470]>orf03039MGEEEMRNKMIIAMSLVVTGVMTYLMFSGLDEDFCHFPWKVFAGFGIMS (SEQ ID NO 504)>orf03040LVEQLTFNQWVTGSSPVRVIYAGLAELADAPDLGSGA (SEQ ID NO 505)>orf03063MPSLRSLKKTDGSCDELHHFDLPVNFFKNTVLGKQTCSGVIREVCQDCFNMLWR (SEQ ID NO 506)>orf03091LHTSFRSSVGHSHTWHQDIVRPILFSRFNDSIVILWQNCPTFNQGIYCYLDCFFPIVSL(SEQ ID NO 507)>orf03096MWSQTLGLIHPLTSLLELPFWMACLKGFGQFCKSLSGLLSFVAECQHLLSLCSRFIRITVLQTSKV (SEQ ID NO 508)>orf03112MLEQARLKVEQQAIKNIQFLEQDLPKNPLEKEFDCLAVSRVLHHMPDLDAALSLFHQHLKEDGKLIIAD FTKTEANHHGFDLAELENKLIEHGFSSVHSQILYSAEDLFQGNHSEFFLIVAQKSLA(SEQ ID NO 509)>orf03113MKHDFNHKAETFDFPKNIFLANLVCQAAEKQIDLLSDKEILDFGGGTGLLALPLTPSQAG(SEQ ID NO 510)>orf03117MVDLQSFFTRKYLNLNSVDAYLILPRLQGHLSYPQDFFLLQDFCFLLPIFLNLSQKEGRNAGKDS (SEQ ID NO 511)>orf03133MRIRNSPFDHILQTIFEFEDRTCQVTCRFEACSSICNDNWEFSQHIISVFQSPSCHTVCDKSDVFCSFL FDKNFASLWIYVVTITDQLCXXIPFIN (SEQ ID NO 512)>orf03142MHKTCLNIWKFLFYQIESLIHQMAADKSPCRIGNRGR (SEQ ID NO 513)>orf03144LNHRFNRQTTKVGRSTIWANGTVNRLIIFVIRSTCIVLINGHSFRCQTSSSTSLPNTKDKVRLITIHLF FQYLSRFVKNCRHL (SEQ ID NO 514)>orf03147MTLHQTFRFQNFEMPCQSSLINFQTLLNRHLVTRRMLQQKQ (SEQ ID NO 515)>orf03151MKKRMLLASTVALSFAPVLATQAEEVLWTARSVEQIQNDLTKTDNKTSYTVQYGDTLSTIAEALGVDVT VLANLNKITNMDLIFPETVLTTTVNEAEEVTEVEIQTPQADSSEEVTTATADLTTNQVTVDDQTVQVADLSQPIAEA PKEVASSSEVTKTVIASEEVAPSTGTSVPEEQTAETTRPVEEATPQETTPAEKQETQASPQAALAVEATTTSSEAKE VASSNGATAAVSTYQSEETKVISTTYEAPAAPDYAGLAVAKSENAGLQPQTAAFKEEIANLFGITSFSGYRP⑶SGDHGKGLAIDFMVPERSEL⑶KIAEYAIQNMASRGISYIIWKQRFYAPFDSKYGPANTWNPMPDRGSVTENHYDHVHVS MNG (SEQ ID NO 516)>orf03156MSNQITVHHSHEHLQKVFTHSWQCNIKNVFIFLKQSLLLMKRNSVGFPTEFTPSILKS(SEQ ID NO: 517)>orf03171MAELNSVITTVTGIENRLGAVILAEIRNIHAFDNPAQLQAFAGLDSSIYQSGQIDLAGRMVKRGSPHLR (SEQ ID NO 518)>orf03178[1501]MEXXXDIRKGRHAVVEKVMGAQTYIPNTIQMAEDTSIQLITGP匪SGKSTYMRQLAMTAVMAQLGSYV PAESAHLPIFDAIFTRIGAADDLVSGQSTFMVEMMEANNAISHATKNSLILFDELGRGTATYDGMALAQSIIEYIH EHIGAKTLFATHYHELTSLESSLQHLVNVHVATLEQDGQVTFLHKIEPGPADKSYGIHVAKIAGLPADLLARADKI LTQLENQGTESPPPMRQTSAVTEQISLFDRAEEHPILAELAKLDVY匪TPMQVMNVLVELKQKL (SEQ ID NO 519)>orf03191LTNLSSVDSEELFQFYRERGNAENFIKERKAGFFGDKTDSSTMIKNEIRMMMGCLAYNLYLFLKQLA GDEVKALTIKRFRRLFLHIAGKYVSTARRHILKFSSLYAYSKQFQALFDTICQINLILPVPYRARGQGKTCLTE (SEQ ID NO 520)>orf03203LFDDRQAINICPPTNGSLRLTSLQVDQNPCPPSTNLNKILARSQFLNHIQQISLSLELLQANLWNLV (SEQ ID NO 521)>orf03207LSVHFCSSHRCLLVRYNDTYSTKKGLKFETFLSVFRYDFLGM (SEQ ID NO 522)>orf03237MDFFNYLLWMICHNHGLHTLLLSKDCVCHTARDKDGNHRIKSVFPTKGQTCYQHDSSIYQERNTTDILT RFLANSQADDIRPTTCDIVSKSKTNPQTHNNTPKKGIDNGILRQGCHRDKLDKEGTHRYRDKGKDGELMANLIPS (SEQ ID NO 523)>orf03245MKIKEQTRKLAAGCSKHCFEVVDETDEVSSKHGFEVVDETDEVSSKHGFEVVDETDEVSNHTYGKATLT WFEEIFEEH (SEQ ID NO 524)>orf03253MKIKEQTRKLAAGCSKHCFEVVDRTDEVSSKHGFEVVDETDEVSNHTYGKVKLTWFEEILEEY (SEQ ID NO 525)>orf03254LFFKDEKQALYTKPKTKSSSFRASKVSNQTIVATTRTDCQVIALNLCDKLENGVVVVVQTTHHIGIDD VIYSKIFQHLTHSIKMSLAFFIKKVQDRRRILYCHLVFFFLRVQDTKRIFLQATLAILRQGLLERCQIVNQGLAVG CTALRISKSVEVQFDTLNTDFLQKMGCHNDCFHIGSWIARTKTLNTNLVELAQAPCLWTLITEHRSHVVELAWLL HFWGEEFIFHIGTDNGRSSFWTEGNMTVTLVIKIVHFLGYDIRCISDRATDNLVMLKNRRAHFCIVIALENLTGK ALNVLPLSRFSR (SEQ ID NO 526)[1516]>orf03260MEQIGKVFRQLRESRNISLRQATGGQFSPSMLSRFETGQSELSVEKFLFALENISASVEEILFLARGFQ YDTDSELRKEITDVLEPKNIAPLEDLYRREYQKHAHSHNKQKHILNAIMIKSYMKSMDERVELTAEEGKVLHDYLFS TEIWGIYELNLFSVSSAFLSVSLFTRYVREMVRKSDFLMEMSGNRNFFHTILLNGFLASIECEEFTNAYYFKRVIEE HFYKENETYFRIVYLWAEGLLDSKQGRVKEGQKKMEDAVRIFEMLGCNKSAEYYRNTTEC (SEQ ID NO 527)>orf03261LIPYFLHFIIFFRKFIKNLPNCQNYEKIEDIYHVEGLL (SEQ ID NO 528)>orf03263MKIKGQTRKLAAGCSKHCFEVMDRTDEVSSKHCFEVVDRTDEVSNHTYGKATLT (SEQ ID NO: 529) >orf03266VVPFSDTFKDRNQVDIFTIKISRCNSSTIGENSWDIHISNSNHRSRHVLVTATDSDEGIHVVTTHSRLD GVRDDVTRC (SEQ ID NO 530)>orf03275MKKFSYPTRQTGEGVKYQSQMVRQWFLIRIFRLFSVA (SEQ ID NO 531)>orf03297VVLDHQNQLFEARFLEHTNPLTRIQLTRVKALRILLSSPPFLVIKGIRTEVDKSC (SEQ ID NO 532)>orf03305VQKLKKAIYKAHLKDSDDFRPETSTPNLFESCLKLCPCFLSS (SEQ ID NO 533)>orf03306 MGALGYYEGFVPYVSNQYKNQAEEEDKPLSDKYIFEKILGKTYAAFKKDQINERVEKLGKLKPITINYN GKSEVIDSKEKLQELMNKAVKDEVAQI (SEQ ID NO 534)>orf03307MMGDGMKEFQFERKQRFSLRKYAIGACSVLLGTSLFFAGMGAQPVQDTETSSALISSHYLDEQDLSEKL KSELQffFELENKLLNLffEH (SEQ ID NO 535)>orf03308MKIKEQTRKLATGCSKHRFEVVDKTDEVSSKHCFEVADRTDEVSNIYTARRR(SEQ ID NO 536)>orf03312VNITKTSIIKAHTTKEDGIDHTFTRFNIMSIFYSTRKIFLDKLNSTNRQFLGYIISTRC YQSFNSVSQSIHTSSSSQAFRFGKHEFRVINRDKSKAILVNHYHLNLAFFISNHIVNSDFCRSSCRCIDSHNWQAF FSRLMKPFIILWFSTICSHDRNTTSCILWRTPAKTDDKVTAMFLQSSYPICDIFTSRVffLYIAKDDIFDSFCIQffF (SEQ ID NO 537)>orf03318MSQDEKLIREQICDVCHKMWQLGWVAANDGNVSVRLDEDTILATPTGISKSFITPEKLVKLNLKGEILE AEGDYCPSSEIKMHIRCYEEREDVRSVVHAHPPIATGFALAHIPLDTYSLIESAIVVGAIPITPFGVPSTMEVPEAI TPYLPDHDVMLLENHGALTVGSDVITAYYRMETLELVAKTTFHGRMLLSTKGIEEQEIARPTLERLFSMRENYKVTG RHPGYRKYNGDGSMKETEK (SEQ ID NO 538)>orf03320MESKKIAKQILIATAVLTSFLGSNLVYADVVQSNSNNRASTETARVTGNNLEKLITKDKEIDKEMTYLSDMDWSSATHGDIDKTKTVQKDAPFTTGNKGEHTKISLLTSDDKVKYFDKGIGTVADSPSVISYDISGQGFEKFETYI GIDQSANSSRSDHAVVDRIEIEIDGKVVYSSSVTNPEGFRYNTQAQFISVTIPQNAKKISLKSFAGEHTWGDEVVFA DAKLIKTVSTQTITPDLLNKGINGGVYLSDLEWVDATHGDDDKSKTVQKDKPFTPGNNGSNNKIKLLIDGKEVEFNK GLGTVASNPSSIKYDVSGANVTRFISYVGIDRSANHLNSDYADIQKFEVVADGKVIYSSDSKYPKGIKYDTSAFLVD VEIPKDTQTIELKSYSGKHTffADELVLGGALFMANGKFKNPNDWSEVDKRREINNEHPLLMMPLYANGEEFNQGKYT FWG⑶ TLTGKWENIPDDLKPYTVIQLHPDDLPKRDGAARDFYEHMLEEAAKYVNPKTGKNEPIPVILTVYTAGNMPY YTSAHWLSTSWIDKMYQKYPNLHGIFSTENYfflWANDIENKAADYLKVSAKNGGYFIWAEQNNGSAIEKAFGKNGKI AFQKSVDKYWKNLIFMFKNTPAAEGNDSTTESYMKGLWLSNHTYQffGGLMDTffKffYETGKffKLFASGNIGKSQGDRQ WLTEPESMLGEEALGVYLNGGVVYNFEHPAYTYGVNNKESLLFSEVIKEFFRYVIAHPAPSKEKVLEDTKVFIHGDY SNKGNGKFFVNVNTDREQTPLYMTGRYNVIPAIPGVLKTDKLKESVSSSRIQIKEITSPEFSSTQARKEYLNKLYPM NYEGDIFAQKLDNRWFVYNYKVNENVKQTGKLKFNSLEMNVEFEPHTYGIFERISNGLKVNLNNFRTNKDSLWSNAQ DANQAKKLPQLTKKGAIKWIEEHYIKDTQFGEKRVTKIVLRGIDKLPTIHSLSGTNNSYDQPSLNFDQKNHMVTITI NSNGNLEFELHF (SEQ ID NO 539)>orf03322MTIYINKDETVFHLAMKDSSYIFRILENGELQHLHFGKRIHVKENYNQLMAYKKRGFEVSFSEEFEDIQ QSMIQNEYSSYGKGDFRHPAFQVQGMNGSRITTLKYQGFELEKGKNRLNSLPSTFDDIGQCAETLTIILTDSILDLT VRLNYTIFPEYNVLVRNTEFLNNSNNKLTLLKAMSLQLDLPDSQYDFIQFSGAWLRERQLYRTSLRPGIQAIDSLRY SSSPQQNPFFMLSRRETTEHSGEVYGFNFIYSGNFQ匪IEVDHFDTARVTVGINPVEFRFLLNPAESFVTPEAIVIY SDQGMNQMSQQLSDFYRHHLVNPNFSQASRPIILNSWETFYFDLGTEKILDLAKAAKDLGIELFVLDDGWFGHRKDD KSSL⑶WVTDRSRLPEGIGFLADEIHKIGLQFGLWFEPEMISIDSDLYKNHADWTIHLLDREKSVGRNQYVLDLTRQ EVVDYLFDSISKIIIKTNLDYIKWDMNRHITDIYSIELDSEQQMEFGHRYILGLYQLLDRLITKFPSVLFESCSSGG GRFDLGLMYYAPQAWTSDDTDPIERLKIQHGTSYGYSPSMMTAHVSISPNEQSGRQTSLDTRTNVAYFSSFGYELDV TRLSVEEKEQVREQIQFYKKYRSLFQY⑶FYRINSPFSCDSASWQVVSKDKCQSILLYAQLNSKLNPGYTRVYFSGL DKDKCYSVSRFDEFFYGDELMNAGIKVSLSNLALCVPEYLTKLFVIEEVVCKY (SEQ ID NO 540)>orf03323MKIENKNVRRNFFWGEGRFYTTDIVNKRAGVMIKNVSKEEFTITLENGIKLSSTHFSAIVREEGDTRIQ VSFVCPSIRLRLIFESRDDVLSKQLVLESSTEVIKSVEVESFEFETEDNIFYPKRQDCIKEMANFSGYYVELGQPVY ANSLFLGMEFPMSENKVDGRHYVSRYYLGTVVNQEKSLWSCIIGGACSYKKEEIQEAFFEYVEGIAQPSYFRKQYNS
wydhmtditeegilksfseirdgfenhgvhldayvvddgwtnyqsvwefnhkfpnglrnikylvngfgsslglwigp
RGGYNGTEIIMSDWLEAHPELNIGSKNLISNDVNVADFNYLNQMKKKMLEYQKEFDISYWKIDGWLLQPDKPDKSGP HGMYTMTAVYEFLIQLLIDLRKERGGKDCWLNLTSYVNPS PffFLQffVNSLffIQISQDVGFTENAGNDINRMITYRD SQYQEFLEKREIQLPMWSLYNHEPIYAVSANTffYMDHQMFASIPDFEAYLLFISTRGNAFffEFHYSFDMFDEERffKA NARAVKWIEENYQTLKYSKKIGGSPEKFEIYGYKCHNQKTSTEILSLRNPAQIKQKIKIENLSIENFTRVIGDFTIQ EDEIELAPYSIVILKK (SEQ ID NO 541)>orf03324MKHTLETINSRIQWFREARFGMFIHWGLYSIPGKGEWIRSHQKLSIEDYEPYFRAFDPKEYNPREWAKQ AKAAGMKYMVLTAKHHDGFCLFDSKFTDYKATNTPAGRDLVKEFVDAVRAEGLKVGLYFSLIDWHHPDFPKYADLNH PMRGNEVYRDEKINFDSYLEYLHNQVKEIVTGYGQIDILWFDYSYEDMVGEKWGASKLIDMVRHYQPNVIVDNRLET SGEGFGSIVTDEITSYA⑶FVSPEQIVPHEGIRNFKGEPVPWELCLTMNNNWAYNPTDYLYKSSQTLIRKLVECVSKNGNMILNVGPDALGRINDSSKKILDNFHRWMSRNGEAIYGCS⑶ENLPKPDWGYYTRNGNTVYAHVFEQPIGPLA LLGISKENVKRMSFLHDGSEVKISESWTTNAYKGICFAQFGEVPHFTYPLPDLIDSVIKIELRE (SEQ ID NO 542)>orf03325MNTHINGISKKGKVLIYGYMLLTILISIFPIAWIFLSSLKADPMKNPGISLPTDFTLEGYINVFTKLHV FTYFWNSFKVVSISVIISIVMISMSSYVIARMEFRGKKLVTSMLYSTLFIPATAMTFPVYRLVNELGIYNTPVALIL VYSCSGIAMSFFIIKNYFEIIPKELEEAAEIDGATYAQTFWKVMLPIARPGILTAAVLAFINNWNEYYWASMLVIDK NELTVPALLGQFTTSFNTNYNGLFSAIVVIVLPPIILFAFTSKYFIEALGGGAVKG (SEQ ID NO 543)>orf03326MAQKIMSLQNRKNQKRRFIFLFLLPTLICFFLFYFYSVVTIFLTSFAKWDYTNLNTPEFLGFDKLFEN YRYVFKEYPFFTEALINSVRWAVIGVIIQVPLAVSVAITLSKKLKGWKISRNLYIVPSIISSAAMGLIFLQIYNPN YGVVNQIIHLFNPSFKDSVLLTPGLNIVAMTGAYIFFAGASTIMILGQIFAIPEEVQEAAILDNITGWRKEWYIT IPMIKGTIKTVSMAATSGFLLYNEVFFLTNGAAGTKSISFVIRELAVASSRTQYARANTIGVIQILGGMLIIVC INILFRERKRLKGEK (SEQID NO 544)>orf03327MNKKSLLKCAVIGLVATFGLAACGTSKDASGGSSSGKEVLEFYHGYHHSEDEWPVAKTMRDLYDKFAEE HKDSGVEFKPTPVNGDLKDIMNNKVASGEFPDVIDLAGNAVSLAAIEQKLVLDLKPYIDSNKLEKNVGLNYKQNQKD GKIYTVHEQLFTMGLWYNKDIFAKAGAKTPDQWNTWDDFTQAMASIRKQDGVYAFGAGEPSIRLFNTVLGTTENGRK LLDKPLTKEGIESKEFADALKMVMKEIQANGSKNAGGDANAYSKDFQEGKSAVFFNGVWASGEMSKNPSLAPGIYPA GVAISSSGGGITISSKMSEAKQKLALEFLKYMTSDDVQKVIFEKVGANPSNENVNVKELSEKSSEATTKILGQAITQ VKNAKAVVPTVSDVWG⑶VHTAIINALTESAAENVDVDQKVKSTQDVLKSLIG (SEQ ID NO :545)>orf03337MNIAIRIILNFFRVMGNHQNSLAMMMGAVVHEFVKFIFTSCIHPRCRLV (SEQ ID NO 546)>orf03338MLLIMSIQTTEPAFSRIATRLDKFIDRTWKTSIKTGNLLRKIGYSQFLTLRICL (SEQ ID NO 547)>orf03339LQNSKTGLDERRLSRSIFPSQGNKFPTINTIIDMFKNRLLIIIEGQILYRNISHYLISPTKAVKNR (SEQ ID NO 548)>orf03344LTSLIPRLMFQKTSQLVSIKILLEGCWIIAIFTEPLR (SEQ ID NO 549)>orf03352MSNSFVKLLVSQLFANLADIFFRVTIIANIYIISKSVIATSLVPILIGISSFVASLLVPLVTKRLALNR VLSLSQFGKTILLAILVGMFTVMQSVAPLVTYLFVVAISILDGFAAPVSYAIVPRYATDLGKANSALSMTGEAAQLI GWGLGGLLFATIGLLPTTFIILVLYIISSFLMLFLPNAEVEVLESETNLEILLKGWKLVARNPRLRLFVSANLLEIF SNTIWVSSIILVFVTELLNKTESYWGYSNTAYSIGIIISGLIAFRLSEKFLAAKWESILFPLVAMAIVTLTILYFPN AQMFLLFSALVGMLSQLKEVPESVFLQETVEENHLVNVYSVLEVISTLAFSVFVLLMSYITDFGYQPFV (SEQ ID NO 550)>orf03353[1564]MSKLLDKILSRE匪LEAYNQVKSNKGSAGIDGMTIEEMDNYLRQNWRLTKELIKQRKYKPQPVLRVEIP KPDGGIRQLGIPTVMDRMIQQAIVQVISPICEPHFSDTSYGFRPNRSCEKAIMKFLEYLNDGYEWIVDIDLEKFFDT VPQDRLMSLVHNIIEDGDTESLIRKYLHSGIIINGQRHKTLVGTPQGGNLSPLLSNVMLNELDKELEKRGLRFVRYA DDCVITVGSEAAAKRVMYSASRFIEKRLGLKV匪TKAKITRPGELKYLGFGFWKSSDGWKSRPHQDSVRRFKLKLKK LTQRKWSIDLTRRIEQLNLSIRGfflNYFSLGNMKRIVASIDERLRTRLRVIIWKQffKKKSRRLffGLLKLGVPKfflAD KVSGWGDHYQLVAQKSVLKRAISKPVLEKRGLVSCLDYYLERHALKVS (SEQ ID NO 551)>orf03357 MFLRCATFKLADSRLNIFTCFFFGEIRFNSRNQVVKAFITDGTVISTIIVRGTVPCNQffTKTCPAAFDI INGDVGFWKAVVDNAK (SEQ ID NO 552)>orf03358MLQITCVVCISCTKVSLVFTWENKDHTTVTQTCVKVNWL (SEQ ID NO 553)>orf03359LRSLIRQITYFITPRTCCINNQTGLDFKYLVCQEITSYNTCNLATFVKEEAFCLHVVGNE GTVLVGTFDVFNHETRIVVTEVKIHSTSYQAFLLQVWLAFQDLILAQNLVRSWCVAHTC(SEQ ID NO 554)>orf03360LHFNQTSLKTASCRLQGYTSSCDSSTDNQEVQGAFLHFFN (SEQ ID NO 555)>orf03375LIHSKMFVKSIRLRKKRVWDKKILILGILYYKFLKSID (SEQ ID NO 556)>orf03379MFASKSERKVHYSIRKFSIGVASVAVASLVMGSVVHATENEGSTQAATFSNMANKSQTEQGEINIERDK AKTAVSEYKEKKVSEIYTKLERDRHKDTVDLVNKLQEIKNEYLNKIVESTSKIEIQGLITTSRSKLDEAVSKYKKAP SSSSSSGSSTKPETPQPETSKPEVKPEPETPKPEVKPEPETPKPEVKPEPETPKPEVKPEPETPKPEVKPEPETPKP EVKPEPETPKPEVKPEPETPKPEVKPEPETPKPEVKPEPETPKPEVKPEPETPKPEVKPEPETPKPEVKPEPETPKP EVKPEPETPKPEVKPEPETPKPEVKPEPETPKPEVKPDNSKPQADDKKPSTPNNLSKDKQSSNQASTNENKKQGPAT NKPKKSLPSTGSISNLALEIAGLLTLAGATILAKKRMK (SEQ ID NO 557)>orf03384MDREILKFFQDLLSILSHNDMITLFCQKCCNSFSNHFLVICN (SEQ ID NO 558)>orf03386MFITLRRICLRACVVEKEQSYLKFLFFQKRPVSFLHVKSVLAGI (SEQ ID NO 559)>orf03387MVKTTDRLEAIGFSFILFENLFKPCQLYLQPQNSVLSNLQLAA (SEQ ID NO 560)>orf03393MTRKLNPSYTNVASATTLTFNQVASTFRKACLDHVVNLTRNNLKGICQLTPLQLHDTRLI(SEQ ID NO 561)>orf03421VKAPIPKAPLAHSFGSAS11AHTIHQKFNLKVPNYRQEEDWTKMGLPITRKEISNWHIKTSQYYLEPLY NLLRERLLTQPLLHADETSYRVLESDSQLTYYWTFLSGKAEKQGITLYHHVLIDLFISYFNPL (SEQ ID NO 562)>orf03430LVSVFYSLLQVDNVDSVTFSKDVLSHLRIPATSLVTKVYTSLKKLFH (SEQ ID NO 563)[1588]>orf03440LIVWILKNHTDLTTYIPNIFLSQTLAINYNLSGFCFQ (SEQ ID NO 564)>orf03441MPYNRKPFSTFHVKRNILHIVVVLIFFIAKRKIFYINY (SEQ ID NO 565)>orf03445MFKKMSNSSRILFYISVNFCDKRIYRTKLYSDTPVNLFKFLFRQKSNCQSVGQTSSINHFFYSWIVFFF KNNLCHSIPSIK (SEQ ID NO 566)>orf03458LADGSGKLAEGGTKLTSGLEDLQTGLASLGQGLGNASDQLKSVSTESKNAEILSNPLNLSKTDNDQVPV NGIAIAPYMISVALFFAAISTWIFAKLPSGRHPESRWAWLKS (SEQ ID NO 567)>orf03464MKNTVKLEQFVALKEKDLQKIKGGEMRLSKFFRDFILQRKK (SEQ ID NO 568)>orf03483LVEQLTFNQWVTGSSPVRVIYAGLAELADAPDLGSGA (SEQ ID NO 569)>orf03487LWVNIDHIRHISCENACLQYFTSIWYIDDFDLDLRVFLLKITSDFFQGFGHFFFLVEILDGHCVIRRFT IVGASAEPKQS (SEQ ID NO 570)>orf03496MKIKEQTRKLAAGCSKHCFEVVDETDEVSNHTYGKATLTWFEEIFE (SEQ ID NO 571)>orf03504LIDVLFINSFIGRICFYCYRRIHATCLFLQLFSIVILNVAHTLKHSIFIVITFISRCRNFIIVRILLEN QFSRNQGIDNRVGQSRY (SEQ ID NO 572)>orf03505MINVNQVSIEVKNTFKNWNFTSSIELTTFSKFSQSPTMT (SEQ ID NO 573)>orf03516MGFSMKLIHDLDMHTTHSTAKMLYNVKAIKNDFSIRE (SEQ ID NO 574)>orf03521MYQDLLRKIAEEKPNYNQEEIQffLLDHLGDPSPEIRDDLVFTSFARGIQEELFTQEQFHFIAEGVSSDG GLDKEIDKIGLPTLERSFRALIYATLLSDDANQQSVFYQELNAGFRNDLSNQGLHYLSKEKDTTGFSSQYGWVHSFA HGADLLTEVVCHPEFPKNRVHEVFDILGQLFKRISIRFTDDEDWRLARVIYEPILQGKLEQEQVASWIKTVDFPIEA REDFYKFSNFRSCLGKSXXIHSLIN (SEQ ID NO 575)>orf03524MGFKVSHFKIPSSHLSINVLRTIENFTEIGQGLLHISP (SEQ ID NO 576)>orf03525VGFFDFGLTNSCRQVRQFTQTVQDFLVCYHQGIVKEGQGYAGICFKFHPSLGNIGKFVIAIVRRLRHKS IVANMAHLNVDLFQFRKGLLEILKSVKIALVITAKLVDVFTSFLDCTQEILTVLV (SEQ ID NO 577)>orf03537LKKAQWGFSNQGPDGLFLVRPTSNRDEIPPRDLAHPQNQLFLSFSQVEKLAWHAPSPLSEFALNISLPL SSPPYLWPFIQSPVLYCASHFSIHFNSFSSHLRLVITISPHLLSSTSLLLHTLCAQHTIHSTDLHHLRTPPPSGLFPLALYTRLAAPTLTYHTLSNIQSLKQQLVXXFIH(SEQ ID NO 578)>orf03548MANDNKSHYLIYRVLGISFEEGENIDLYQNKGRFLYKYAGSFLEEAAVLSFNEKFGTENT(SEQ ID NO 579)>orf03553MVNAMHFSFSILIEGNSRKVGICLLNRTHTRFKLSQAIYL (SEQ ID NO 580)>orf03562MSQQLSDFYRHHLVNPNFSQASRPIILNSWETFYFDLGTEKILDLAKAAKDLGIELFVLDDGWFGHRKD DKSSLGDWVTDRSRLPEGIGFLADEIHKIGLQFGLWFEPEMISIDSDLYKNHADWTIHLLDREKSVGRNQYVLDLTR QEVVDYLFDSISKIIIKTNLDYIKWDMNRHITDIYSIELDSEQQMEFGHRYILGLYQLLDRLITKFPSY (SEQ ID NO 581)>orf03572VKEEKKAIVLGADNAYMDKVETTLKSLCVHHYNLKFYVFNDDLPREWFQLMEKRLETLNSEIVNV (SEQ ID NO 582)>orf03574MKIKEQTRKLAAGCSKHCFEVVDRTDEVSSKHRFEVVDRTDEVSSKHRFEVADRTDEVSSKHRFEVADR TDEVSSKHRFEVADRTDEVSSKHRFEVADRTDEVSSKHRFEVADRTDEVSNIYTARRR (SEQ ID NO 583)>orf03576MEXXXFKAGAKFFWAKLGLESLEAKEILRDGGWDDIVKNRCIKREQPRLIEEA(SEQ ID NO :584)>orf03588MILLQNKSFCYSISQKETSLCHANVVTLNLHEALLNQISDNFSIKSSKRLSKFFLKSRHGNPGFLAES QEHFFFHLLLLTQVIFCNTSIAFLNRTEIMTNGTMIFIAYSIDITRCPCTNTIVFSIVPVHEIMTTFKAGFGEIRN LIMLKTRSLQLCNDVLKHLRF (SEQ ID NO 585)>orf03612MDREILKFFQDLLSILSHNDMITLFCQKCCNSFSNHFLVICN (SEQ ID NO 586)>orf03614MEDHLLINAVDEFRSISFFQFFKHAFFHIFLVKTNILSPKTNSLIITKGSRTTCFFFACQIRSSWYLKN QTNIQ (SEQ ID NO 587)>orf03620LFIRKKHTWINLTPKQTIFSQMNAQFFINFTRRALKRTFITFTSPTWQFPHIGPGNACLIIT (SEQ ID NO 588)>orf03637LNIAYTDNPAHIFGKIFHDNLLALLIIFDDVTCKACLRQDKVNSGLFLDSLFNSGCKGVGFSLVRLVIS I (SEQ ID NO 589)>orf03641 MCELDILHDSLYQFCPELHLKRLNSLTLACHALLDCKTLTLTELGRNLPTKARTKHNIKRIDRLLGNRH LHKERLAVYRWHASFICSGNTMPIVLVDWSDIREQKRLMVLRASVALHGRSVTLYEKAFPLSEQCSKKAHDQFLADL ASILPSNTTPLIVSDAGFKVPWYKSVEKLGWYWLSRVRGKVQYADLGAENWKPISNLHDMSSSHSKTLGYKRLTKSN PISCQILLYKSRSKGRKNQRSTRTHCHHPSPKIYSASAKEPWVLATNLPVEIRTPKQLVNIYSKRMQIEETFRDLKSPAYGLGLRHSRTSSSERFDIMLLIALMLQLTCWLAGVHAQKQGWDKHFQANTVRNRNVLSTVRLGMEVLRHSGYTIT REDLLVAATLLAQNLFTHGYALGKL (SEQ ID NO 590)>orf03644MXXTKSSCLITTGRNDSPSTCLPRVASNNDRFSSEFRIIPDFHCSKKGIHVNMDDFS(SEQ ID NO: 591)>orf03650MHFHIIKLVNHFQLLIKLNRISHPNLHIKSSFLSLVLLFYQKEQDFAIMVI (SEQ ID NO 592)>orf03660MDRGESLSDCVCMAGYEPANSSRLSIEGTYENKLYKLISSKYHTTGNDIMVCVPCGYTKYKETPGPHA CTSCPGRTHAASTTNTNQDQCNRCPPGYYETNDPSYPCDVCSPNHICVGSDPMDPALMLYSGKRIKCDKNSVTLVP FEENVHLASCLCDKGYMARTRTGIVKCEAVPKNTYKDVVGNVGPTNCPPGSYTLKIGATDVSECVCKRGMFFDKD NKRCTVCPVGMYCLGGRLPNGEHMLPMMCTDGNAVTKDGGATSPGECLCKPGFYLRQDGPGGCVECPENTYKSFI SNENCSPCPRIL (SEQ ID NO 593)>orf03667MXXAFCLPVFAHPETLVKVKDAEDQLGARVGYIELDLNSGKILESLRPEERFPMMSTFKVLLCGAVLSR IDAGQEQLGRRIHYSQNDLVEYSPVTEKHLTDGMTVRELCSAAITMSDNTAANLLLATIGGPKELTAFLHNMGDHVT RLDRWEPELNEAIPNDERDTTMPVAMATTLRKLLTGELLTLASRQQLIDWMEADKVAGPLLRSALPAGWFIADKSGA GERGSRGIIAALGPDGKPSRIVVIYTTGSQATMDERNRQIAEIGASLIKHW (SEQ ID NO 594)>orf03668MARFIRSQTLTLLEKLNELDADEQADICESLHDHADELYRSCLARF⑶DGENL(SEQ ID NO 595)>orf03669MTVRELCSAAITMSDNTAANLLLTTIGGPKELTAFLH 匪⑶ HVTRLDRWEPELNEAIPNDERDTTMPV AMATTLRKLLTGELLTLASRQQLIDWMEADKVAGSLLRSALPAGWFIADKSGAGERGSRGIIAALGPDGKPSRIVV IYTTGSQATMDERNRQIAEIGASLIKHW(SEQ ID NO :596)>orf03673MKIHKTVNPVAYENTYYLE ⑶ KHLIWDPGSHWEAIRQTIEKINKPICAILLTPAHYDHIMSLDLVRET FGNPPVYIAESETQLAPKPLPNNPLGPPXHSFIN (SEQ ID NO 597)在一些實(shí)施方式中,優(yōu)選的0XC141抗原選自以下多肽或其免疫原性片段
orf00045(SEQIDNO 53)、orf00068(SEQIDi NO 65)、orf00074(SEQIDNO70)、orf00223(SEQIDNO 99)、orf00229(SEQ [DNO 104)、orf00360(SEQIDNO :117)、orf00506(SEQIDNO 135)、orf00781(SEQIDNO 177).、orf00785(SEQIDNO ;178)、orf01068(SEQIDNO198)、orf01446(SEQIDNO235)、orf01447(SEQIDNO:236)、orf01449(SEQIDNO237)、orf01455(SEQIDNO242)、orfO1460 (SEQIDNO ;■Ml),orf01461(SEQIDNO248)、orf01463(SEQIDNO250)、orf01464(SEQIDNO :251)、orfO1466(SEQIDNO252)、orf01467(SEQIDNO253)、orf02661(SEQIDNO :433)、orf02690(SEQIDNO439)、orf02698(SEQIDNO444)、orf03318(SEQIDNO538)、orf03320(SEQIDNO539)、orf03322(SEQIDNO540)、orf03323(SEQIDNO =541)、orf03324(SEQIDNO542)、orf03325(SEQIDNO543)、orf03326(SEQIDNO :544)、
orf03327(SEQ ID NO545),orf03562(SEQ ID NO:581)、orf03660(SEQ ID NO :593)。[1657]6由INV200鑒定的序列>orf00004LKGVDDFLFIFEEGFKQGGKARADRDYSGVSSLRNSSKVYLEFLY (SEQ ID NO 598)>orf00005LCSALKNSYDIELIKVLSNKAHLYLPIETVTPQTVSTS (SEQ ID NO 599)>orf00006MRVAETSIVKKNHQIPCIINQKIAQKLIKKTSMTDIDHQLSISTSTVIRKINDFHFEHDFSRLPEIMS (SEQ ID NO 600)>orf00010MFKSNLSLSQSLPHKDFFFFKRIIHLFSLFLLIDFIIIS (SEQ ID NO 601)>orf00015VEEVEVAEVKNARVSLTGEKTKPMKLAEVTSINVNRTKTEMEEFNRVLGGGVVPGSLVLIG⑶PGIGKS TLLLQVSTQLSQVGTVLYISGEESAQQIKLRAERL⑶IDSEFYLYAETWQSVRAEVERIQPDFLIIDSIQTIMSPE ISGVQGSVSQVREVTAELMQLAKTNNIAIFIVGHVTKEGTLAGPRMLEHMVDTVLYFEGERHHTFRILRAVKNRFGS TNEIGIFEMQSGGLVEVLNPSQVFLEERLDGATGSSIVVTMEGTRPILAEVQALVTPTMFGNAKRTTTGLDFNRASL IMAVLEKRAGLLLQNQDAYLKSAGGVKLDEPAIDLAVAVAIASSYKDKPTNPQECFVGELGLTGEIRRVNRIEQRIN EAAKLGFTKIYVPKNSLTGITLPKEIQVIGVTTIQEVLKKVFA(SEQ ID NO 602)>orf00018MGVSIFLALFYMIPALYFLFRIGKKWELPKKVLILSLLGGMFLSGWLSSFANTYIHDFMNCTPKVRQKK SNFWGVLL (SEQ ID NO 603)>orf00019MKLSYEDKVQIYELRKQGQSFKQLSKRFGVDVSGLKYMVKLIDRYGIEIVKKGKNRHYSSKLKQEMMDK ALLEGCSQRSISLDYALPNQGMLSFWPAQYKKNGYTIVEKTRGRPAKMGRKRKKTWEEMTELERLQEENERLRTEVA YLKKLKELEERDEALERERQRQLEKWFQEDFD(SEQ ID NO 604)>orf00020MVSGGFRLDFLLETARLARSTYYYQLKQLDGVDKDKEIKTEIQGIDNEHKGNYGYRRIHLELRNRGFVV NHKKVQRLMRILGLTARIRRKRKYSSYQGEIGKKAENLIQRQFEASRPMEKCYTDVTEFAIPNSTQKLYLSPVLDGF NSEIIAYHLSTSPNLEQVKSMLEQAFTEKYYENTILHSDQGWQYQHDSYHRFLESKGIQASMSRKGNSPDNSMMESF FGILKSEMFYGYEKNFRSLENLEQAIVDYIDYYNNKRIKVKLKGLSSVQYRTKSFG (SEQ ID NO 605)>orf00024VNIATLQNGHILGWQIQHIANKLTSNFWIAKDFLSYQVIGffANARMTYSHISSLFIISQF(SEQ ID NO 606)>orf00026VSITFSLTNFFKILINLTAQVSPQVIDEKILMMDLNLNNYLSTVIQLRQDVYTGIKILHRVRHGE (SEQ ID NO 607)>orf00027MSRYSYSLDSRKIVFEISCFKEKKASLTLFFHLFESSIMKLATQPSYSSFYSELK(SEQ ID NO: 608)>orf00033
112[1681 ] MKIKEQTRKLAAGCSKHCFEVVDRTDEVSSKHRFEVADRTDEVSSKHRFEVADRTDEVSSKHRFEVADR TDEVSSKHRFEVADRTDEVSSKHRFEVADRTDEVSSKHRFEVADRTDEVSNIYLRQGDVDVVEEIFEEY (SEQ ID
NO 609)[1682]>orf00034[1683]MKPGAEGWKDERSQDIEEKDNGDGLGYFLFLSMDNRRCRCNGRTPTDRRTYSNQGSQFCIQGKEALEEVGNNQGY(SEQ ID NO 610)[1684]>orf00035[1685]LPNCEDLRDIETKTKQDNGILEQFLGTKGQSNIQLFIRREKGM (SEQ ID NO 611)[1686]>orf00044[1687]LSLLDLRGSLCLRIYLHEPLITTVSQDFTSLSDISHF (SEQ ID NO 612)[1688]>orf00047[1689]MDFKSFIIGLVVGIFGPYMDDLIRKKFLKSSEKKTEKSVKK (SEQ ID NO 613)[1690]>orf00093[1691]MTYEYKSHIYLAETVLNVKDLASQTTFYQQVIGLEILSQTETESILGLGGKVLVQLIQAQESGEVREHX
XXFHSLIN (SEQ ID NO 614)>orf00103MVSNLVFIGNCNFHNTVI FHLLNRLNQGPLQILSQNHDKGRRLSWIFKSRLGQLNASKNWMGRKEQAM ALAIAADLQDQLLFKKAD (SEQ ID NO 615)>orf00113MKFNPNQRYTRWSIRRLSVGVASVVVASGFFVLVGQPSSVRADGLNPTPGQVLPEETSGTKEGDLSEKP ⑶TVLTQAKPEGVTGNTNSLPTPTERTEVSEETSPSSLDTLFEKDEEAQKNPELTDVLKETVDTADVDGTQASPAET TPEQVKGGVKENTKDSIDVPAAYLEKAEGKGPFTAGVNQVIPYELFAGDGMLTRLLLKASDNAPWSDNGTAKNPALP PLEGLTKGKYFYEVDLNGNTVGKQGQALIDQLRANGTQTYKATVKVYGNKDGKADLTNLVATKNVDININGLVAKET VEKAVKDNVKDSIDVPAAYLEKAKGEGPFTAGVNHVIPYELFA⑶GMLTRLLLKASDKAPWSDNGEAKNPALSPLGE NVKTKGQYFYQVALDGNVAGKEKQALIDQFRANGTQTYSATVNVYGNKDGKPDLDNIVATKKVTININGLISKETVQ KAVADNVKDSIDVPAAYLEKAKGEGPFTAGVNHVIPYELFA⑶GMLTRLLLKASDKAPWSDNGDAKNPALSPLGENV KTKGQYFYQLALDGNVAGKEKQALIDQFRANGTQTYSATVNVYGNKDGKPDLDNIVATKKVTININGLISKETVQKA VADNVKDSIDVPAAYLEKAKGEGPFTAGVNHVIPYELFAGDGMLTRLLLKASDKAPWSDNGDAKNPALSPLGENVKT KGQYFYQLALDGNVAGKEKQALIDQFRANGTQTYSATVNVYGNKDGKPDLDNIVATKKVTININGLISKETVQKAVA DNVKDSIDVPAAYLEKAKGEGPFTAGVNHVIPYELFA⑶GMLTRLLLKASDKAPWSDNGEAKNPALSPLGENVKTKG QYFYQVALDGNVAGKEKQALIDQFRANGTQTYSATVNVYGNKDGKPDLDNIVATKKVTIKINVKETSDTANGSLSPS NSGSGVTPMNHNHATGTTDSMPADTMTSSTNTMAGENMAASANKMSDTMMSEDKAMLPNTGETQTSMASIGFLGLAL AGLLGGLGLKNKKEEN(SEQ ID NO 616)>orf00118MSLQIKLKKLAKELSKLLKDSNLETVDKDVLENSQKELQKAVLFLADEKGSEHTEAEVIDNLKEVIAKL KANA (SEQ ID NO 617)>orf00129VGRFFGSSQTSDEFFFSFDSSIVKELSEIVHGFDTVSFR (SEQ ID NO 618)>orf00140[1701 ] MKIKEQTRKLAAGCSKHCFEVADRTDEVSSKHCFKVVDGTDEVSSKHCFEVVDRTDEVSSKHCFEVVDR TDEVSNHIRQGDVDVV (SEQ ID NO 619)>orf00146MNDDDSRCIHIERDGKTIEFGYLNISSTDRNTSHADGLVGIFNSNFSGVRVRGIAVFLNGPDNLDTTLV GNFQTIWNFRIICIHS (SEQ ID NO 620)>orf00147 [1705]LEFNFCRSIIKNGRDNLPNTNSTSGMATRWANHNWSDDIKDRLKTK (SEQ ID NO 621)>orf00152MSCNCAFYRSQFFDVNSVSNYHSHQKELRFPNSILFTYFVKVA (SEQ ID NO 622)>orf00156MSKEKVILAYSGGLDTSVAITWLKKDYDVVAVCMDVGEGKDLDFIHDKALKVGAVESYVIDVKDEFATD YVLVALQSHAYYEQKYPLVSALSRPLISKKLVEIAHQIGATTIAHGCTGKGNDQVEYQIAVAKKANEAKK (SEQ ID NO 623)>orf00157MRYDFGKVYKEIRESKGLTQEEVCGGVLSRTSLSKIESGKTTPKYENMEFLLRQINMSFEEFEYICQL YQPSQRTEIMQTYL匪RSIIGTSDLVNLFQKCQDYLKTHHDLPIEEIRDMLEVVIYIRQHGAGELSDHAEQVVKKL WRKIEKQDTWYESDLKILNTILFSFPIEYLHLITGKILQRLEVYKNYQHLYDLRIAILLNLSTLYLYNQDK匪CKQI CYTLLEDAKNKKSYDRLAICYVRIGICTDDSKLIQKGFSLLELTEETSMLSHLKKEVEIYYQAKER(SEQ ID NO 624)>orf00158MKIREIIGTDMYGTTVSGIVSGLNKLNFTVKAVRVALEDLTPKLTFPAILQVKNDLGQNHFVVLHSIKE KINGTRITK (SEQ ID NO 625)>orf00159MELVLPNNYVVIDEEEMMYLDGGAIYIPRWAITGAITGAAYAALAAAGGGGLQLVLASYGLRSALVAGI VKGLGVLGIHIGNAFANTVIRSIASAGIGAGADWIFTNIIDGWDGRRDNQLRIG (SEQ ID NO 626)>orf00161MATITNALNIAATVAEVFSLGGAIAYGLDIVDGKFDGYLWA (SEQID NO 627)>orf00162MKDDQKYLLAGLYSLLVAIFYFPLIESKGIFVSILMAVLLLYLIYFIATVIHIVIIKFIRKKSFKYLVL YPFTYDGSWRFQPINLLYFPEMVRDVIPINLVQEYCQGQPYGLLKKMLKRIRLSREIALLLATIIVYFFTHRILPLS VFTFMFSYILLFVQSYLGSNTAWIGNRRLIIDDEFEKILLSKSYIKEISSARYSEYLTCEYKNPTPIILIAIFENLL DSYLLQNQSEVDLDIFYKVLPLLYKEKYTMGFNYFVSLNYLLYKVGFLGIIYDNEALRDLSKQYLNKNISELQDGSF EGGIQDAVASKQIVVINEFIACLNSKCMPSQYDRFFYKDRPYIFSRKSSIKG(SEQ ID NO 628)>orf00163MKNKRYFFDTILIILLLISTIFCVSPVFIKLDILGTPSHAILTFVLAIPLFYILSQCLHT LLLLVSSIFCKLRPIYFYFIFVIIIGARKYYRILFHQLMGFSPGIAVFYKESQTTKNLFKFYYFLYFTTLISYYFFF TFVYDKSLLLPLIPFSIIIALVQKLYRIENQQLFLLKSKVLTILESKRDCEFNLQDYHEIWKLQSKSELPCVALSYI SLIKPYLSESVREQIDLLEVKRFKKINHPISLYGMLDVIKLNLYLRHYNEKNKYESMLNKILEVRPDFVLIEQNIDD SLNSSQPLSLSLAISEIQLLLEVYIGIKHVSIRR (SEQ ID NO 629)>orf00164[1722]MIRKPIIFLLMLPIWGLWIELHLLVSNLQLNLEIPFDFVVSTSLTFFVLILSKIVLDILYALKDLYKK EALITIFPFIFIGRKKVNVRFSPYFSFHRKSLSPDDLRSRIIWSFILEIAIILVFILKIPFAIIMLTTIFFWTIMD INHLVFNKTEFLFNQNKWQKEDSFESDLTKTLKDKIQKSELSYSDLMSLQLYDAMNQSTFLTDSELFEDILKKIE DSHNTLLCTGLVELLLYEISISNNNNWQEKVDKIRIQLIRINQLDFFYYTSWLRQNFDFCMNREYHKMKSRKLLL SNKKIV(SEQ ID NO 630)>orf00165MELVLPNNYVVIDEEEMMYFDGGAYLSKRACQGICAALAMSSGTFIALAGAAVLTKKLINYIKVGGLGG WLIGAAAGKIAYYIGYGVLNRGCDINGNPYPWDGFISATVR(SEQ ID NO 631)>orf00166MSNVDKIRKIHIIVCWVYIFLSFRAIINDTEYFLLIFLAFIYSIVSLPLYSVKNKIVSICLAINSILLM SFPILINKFFPESFLTYTVLISVFITELIIFHLIGKDFDIKLTNEYKKISQFRSKVSQSPWIKYLEISSFILTIFPS ILYGTVDNHVLTLIFLIKICVDTTIKFLFIRLFDTSTLMKRRIFFLFALDVIAYLFLGYLLVIQKAGYLFSVLLLFS NFSVPFIKEKEYELFKNSK (SEQ ID NO 632)>orf00167LFNEIKKTSSLIGNVFIGMKEDDAMFKKRIEKGKSSVFIFLE (SEQ ID NO 633)>orf00168MNKKKMILTSLASVAILGAGFVTSQPTFVRAEEAPVASQSKAEKDYDTAKRDAENAKKALEEAKRAQK KYEDDQKKTEEKAKEEKQASEAEQKANLQYQLKLREYIQKTGDRSKIQKEMEEAEKKHKNAKAEFDKVRGKVIPSA EELKETRRKAEEAKAKEAELTKKVEEAEKKVTEAKQKLDAERAKEVALQAKIAELENQVHRLETELKEIDESDSE DYVKEGLRVPLQSELDVKQAKLSKLEELSDKIDELDAEIAKLEKDVEDFKNSDGEYSALYLEAAEKDLVAKKAEL EKTEADLKKAVNEPEKPAEEPENPAPAPKPAPAPQPEKPAPAPAPKPEKSADQQAEEDYARRSEEEYNRLTQQQP PKAEKPAPAPVPKPEQPAPAPKTGWKQENGMWYFYNTDGSMATGffLQNNGSffYYLNSNGAMATGffLQYNGSffYYL NANGAMATGWAKVNGSWYYLNANGAMATGffLQYNGSffYYLNASGAMATGffAKVNGSffYYLNANGSMATGffLQYNG SWYYLNANGAMATGWAKVNGSWYYLNANGSMATGWVKD⑶TWYYLEASGAMKASQWFKVSDKWYYVNGLGALAVN TTVDGYEVNANGEWV (SEQ ID NO 634)>orf00190LKKRMNRWQFLLNQSKEMVGILLLKMKEQELIEFVVNL (SEQ ID NO 635)>orf00191LIKVIKRKAFGFRNFNNFKKRILMTLNIKKESTNFVLSRL (SEQ ID NO 636)>orf00195MTYNEKRLTNSLERVHMEQLKNTTDLLGLEDKNIKILSVLKYQTHLVVQAKLDSPAPPCPHCQGKMIKY DFQKASKIPLLDCQGLPTVLHLKKRRFQCKNCLKVVVSQTSIVKKNCQISNMVRQKIAQLLLEKQSMTEIAHRLAVS TSTVIRKLREFKFETDWTKLPKVMSWDEYSFKKSKMSFIAQDFESKSILAILDGRTHAVIRNHFQRYQREVRELVEV ITMDMYSPYYRLAKQLFPKAKIVLDRFHIV (SEQ ID NO 637)>orf00196MGYSLKKSRTYCEQDPEKVNRFLKELNHLSYLTPIYIYETGVETYFYLEYDRALSRQLVSLEEDIII (SEQID NO 638)>orf00201MRFYCEAYEVITEEKKVYFNDIELEVKYSSVEELFIICEKLLDKKKVSFFYVDEKPLRYLLFDYIFLLVLAKKNIPILDGVSNKQVDPTLLHHFSLEIEKNFIDFCYKNMDLILKTQSISLCHREELIIVDVSDDSKFGVFYKRFR TLVDKNNGKYVCVYNFSRVSDILQNWKNYCNRKFSVTFTESQFELFKLLYNQKNFKTISLLFGKKIVAGGIIYYSDL TNIEYFCIFWWDSMFGKDSIGKYVYVEEISRCHFLDRNYSFCYGLQDYKSKLIKYFLE(SEQ ID NO 639)>orf00202METRNLISYSLTDIFETDKIRIELLGEIYYKNIKLELHEFAGLYKIYGISLIKNITGMFLIIIFDTKTK ELKIFQDITTSYFNLYYTVYGGVFYYSTSLKKVMKLSHVPVTLNNKKIQEFMRNGFILDSNTLVTEINKLEYFSYIS VNNTLRICGIDYNDSNNFTKEQVLKNWDSMLRESILRVYSEAGEANITLSSGFDSNYILYTLANYTNSSINAFCIGG EKGINEIPEVTKIAKFYGINLLVDTVMSQDLEYFPDIVWRLEGSLFECGVILQYYLGRLLFQKGNTSILCGESADEI MTFKYHSVNYNQFCNDKQKSVYFSYSDYPFYVTNSIVLKKNSLLLHSFGIHPRYPYKMSEIVEMSKKISDLNDKKEF HKKNCELRFQDSVLDNINSVPGTTHLFSCLNIQTLVKIILYIFRYNSCMKIFNFRDKELIFFNKIVNGLIQNIEENL EDDIERILKYLYICLFNEIFIIKNKVNFFDDVEFNQTLSEFLDKL (SEQ ID NO :640)>orf00204MKFFCENNLNITFFDTFSEIKNNIDYYIIALPTDYDEKIGSFNTYEIEQTVSKILRVKPNGK11LKSTV PIGFSNKLKRLFDTKNIIFVPEFLREGCSIYDNLYPSRIVVGDETVEGRKIAELFLSISTHSTANIKNVMLVSPTEA EAIKLFSNTFLALRVAFFNELDSFAERRSLNAEVVIKGVCLDPRIGNFYNNPSFGFGGYCLPKDTKQLKKEFIEINA PVIEAIDISNTNRKQFIVKQILERKPKIVGIYKLGMKYNSDNYKESAILSIINELLIVGIKILVYEPNLNVSIDNVI FEKNFELFTKQSDLIVANRWDRGLEAYKDKVYTRGIWIRD(SEQ ID NO 641)>orf00206LEEESFIMENTEFSLELDVTEVATEQDYVSSGVTSTGCCKN (SEQ ID NO 642)>orf00207MFKIKDNYIYRQCVNDSILIEKLNENNLEIFFDSKIFQEMLMVANPRFFNELTKEKIYQNSTFRNYAKR SLTRATPFGLFSSVGVGSFSKVSYPQQIRENYSKKVSVSGEWISSLCMMLENEDSVLLQLHLQWNQKVLELSDKYQL NNINYWGVSEQSRDILIKKTALLEFIKKLTYKSEVSVLDLVQEIQTKSPNLETQKIIDYLRNLIISEFLFTNLRKVV INHNCLDNLIYILSSINEQTKLTTDLLQLKSCIEKYSKSELGEGILQYAEICEKMSHIFNEEKQRYLKVDLVNSYDS LLPKDLKKTLEDFVNFISRINLGKDYRNKELISYTEKFVEKYGEYVEVPIKQLLDSKLGLGIPKQNLEPYSILSSVA EQTFLSYLSKEIFKAVKNNKKEIDISNIPPELLYPNLDRFAVNQFELYCEMKNFGEQPVISIVPNTGSDMIGKSIGR FASYFLNSNIELDSRVDNVELIEFPSDNKNLNVMSSHHGHSKKLLLSYEDDFDIDSLELDFLVVGVERVNEHYKLYF RDLRTDLIVNFVTTSMLNHKSIGVFSHLARFLLTVSLEWQDNPFSLFRVIENLDFLPYIPRIKYKNIILSEEKWILS DVDKKDMSTISQWKKFFDVPSLLYFHKDDERLLIDLKNSLDVQWILKQNVDKLHFTRFDKIDGKNCEFIFGFENPRN SVYPHSVSEKTVRRIENDFYKDYVKTFSSDWIYFKLYGINSSTMPELRENLLIFTDELLAEKLVSDFHFVNYNDGGD GSIRLRFKIMNEDDFEKLRYRIIHWIDFLLNHYFCKDVSFNLYEREVERYGGIGFLTVCERIFSIDSYLVLKLFSKK VLKVDDYLSVLHSIFIYIRLLGISPKQLLKLMKDTFTQNIYRKSFKKVFPNNAKVIKEFKQYFEDQSKFDIFNEVFK SFSPIEKHFEYKNDMIHSLLHMHMNRIGIFSLNEKEYLYFVRYILEVLNNYEKYN (SEQ ID NO 643)>orf00208MRNIIKKYDEIINKVDSLVLDNNIIDLLQRSCYTENRSYLSEYPSIIIYLSYRLANCDDNEHSKLLYNR VNYYLHELLKSIKLNSRNNISMCYGFSGYVYALKLLPKRSKEYSKLLETLETILVSLTRDRLSEIKKSNKVKEEYID VIQGVSSVGKYFLSKDKLTSNQELLLKGVLNYLAGVINNKPTIYPEYMPNEKLKRKFPNGYINLGVAHGILGPLYVL ALGFKKFNMPEYLISLKKGLSYYEKTFQTNKIGKIIGWNGRVSAEVESEKFEYNLSWCYGSLGMARVLYNISKIIDI PKLQELATDVFHSSIYYLNSSEILNNAICHGRSGIMLLFNLMYLDTGESQFKAISDNLFKEIVNKATDSEYIFVERDIYFRGVNYDEVIEYIDFCLLNGVSGIVLALMAQRTGNASPLAEMFFMQ (SEQ ID NO 644)>orf00209MKKILNNKLYMKVLVSDLISNF⑶TLYFIALMTYVTEIKSSNLAISIVNISETIPILFTIFFGIIADRT LNKVGMIIKTLWIRTILYLLVAVVMNFKESILVVILASIVNLISDTLGQFENGLFYPISNRIVKKSDREETMAFRQT ATSTMNIVNQSLGAFLITFLSFFHLALINSLTFAISLLITLAIKSQINNFYIDKTPSTKVSKVDFKATFSDIISNLK LSLKHLFSLTNMKTVLLVIPILNGSLAIIIPLAVVNLSKSSALTIISSATTISVLGISTVSGGILGGTLILISKKFK NLSIENLLKMNLMTILLSFIAFYYQNIYFIVLTLFLSSVFVSALNPKIGAIIFNNLDETKLATIFGGMVTYFQLGDV VSRLLFSTLVIYLSYTYIAVIYMILVLIVAIYTFRRVQTTS (SEQ ID NO 645)>orf00213MKIKEQTRKLAAGCSKHCFEVVDRTDEVSSKHCFEVVDRTDEVSNHTYGKVKLTWFEESFEEYK (SEQ ID NO 646)>orf00217LKSSILSKMGDFSVRYCNLVGTVLFGVVLIAILRLVF (SEQ ID NO 647)>orf00246MGLDVGSKTVGVAISDPLGFTAQGLEIIQINEEQGQFGFDRVKELVDTYKVERFVVGLPKNMNNTSGPR VEASQAYGAKLEEFFGLPVDYQDERLTTVAAERMLIEQADISRNKRKXXIPFIN (SEQ ID NO 648)>orf00270LNTSYSFGKKDQFALEHCFCIKLSIFARAVTLFVSCIN (SEQ ID NO 649)>orf00291MLIGEGYRTFPVLIYTQFISEVGGNSAFAIMAIIIALAIFLIQKHIANRYSFSMNLLHPIEPKKTTKGK MAAIYATVYGIIFISVLPQIYLIYTSFLKTSGMVFVKGYSPNSYKVAFNRMGSAIFNTIRIPLIALVLVVLFATFIS YLAVRKRNLFTNLIDSLSMVPYIVPGTVLGIAFISSFNTGLFGSGFLMITGTAFILIMSLSVRRLPYTIRSSVASLQ QIAPSIEEAAESLGSSRLNIFAKITTPMMLSGIISGAILSWVTMISKLSTSILLYNVKTRTMTVAIYTEILRGNYGV AAALSTILTVLTVGSLLLFMKISKSNSITL (SEQ ID NO 650)>orf00292LIIIASMSAPFVGAYSWVLLLGRNEVITKFLTNALYLPAIDIY(SEQ ID NO 651)>orf00293MERKKLNIWTVSSFFLFLTYPIFLVYPIVTVLKQALIHEGQFSLANFVTFFSKAY(SEQ ID NO: 652)>orf00295LLSTTEFIGLSIRILSNLHEFKILVGLLNQFFFWNLLLHKTKSNVVSDSQMWENSVVLENHPDIAFAGF HIIDFCIIEVKFSTFDTVETCNHTKKGRFPTS(SEQ ID NO 653)>orf00314MITIKKQEIVKLEDVLHLYQAVGWTNYTHQPEMLEQALSHSLVIYLALDGDAVVGLIRLVGDGFSSVLV QDLIVLPIYQRQGIGSALMKEALEDYKDAYQVQLVTEETERTLGFYRSMGFEILSTYNCIGMTWMNRKK (SEQ ID NO 654)>orf00325MKIKEQTRKLAAGCSKQCFEVVDRTNEVSNHTYGKATLTWFEEIFEEYNTNLEYKQPICSQEKA(SEQ ID NO 655)[1773]>orf00359MVDNIPKRVNDVIRQAGNNAKTSRPHVGIGKSHISVSFLFPYHTANRIKNQEKVIF(SEQ ID NO: 656)>orf00375LFDLLDHGLDTVLVCHVTDISMGLDANFTISFNPFIDQILIDIVKDNSSAGFSVGFGNSKSNSIRSA⑶ ESNFSF (SEQ ID NO 657)>orf00387MKSLARLLIIHVFISIFLFFALTSGAISHTVLLLLLLFLPALNKGLEKIQSKRIPVLNAALFFLLISFP QLLTNPVQWKFSIFLVVTIISSLAYFYNFYQVVKEVDQKQLI (SEQ ID NO 658)>orf00390LEAAGEIETEFQGWIVLVVFNHIDSLSRDTDILGEFELGNTQFLAKFFHTIHLISFLIYVVYI (SEQ ID NO 659)>orf00403MEGVNHVDIIKVSCCSFISQVNWMMKGKIPNREGFKFSVARFDAIDLVVVHIGHTRCQFSRTGSRSGYD NQVATGFDVVVFAHAFWGNDVIHIRRISFDWIMKIRINSVFLKLVAEGICSGLASVLCNDNGTNKNP (SEQ ID NO 660)>orf00404MFNVASINGNHNLNLLFQFLQELDFVVRFITRKDTSSVEIF (SEQ ID NO 661)>orf00409MIDIHSHIVFDVDDGPKSREESKALLIESYRQGVRTIVSTSHRRKGMFETPEEKIAENFLQVREIAKEV ADDLVIAYGAEIYYTLDALEKLEKKEIPTLNDSRYALIEFSMHTSYRQIHTGLSNILMLGITPVIAHIERYDALENN EKRVRELIDMGCYTQINSYHVSKPKFFGEKYKFMKKRARYFLERDLVHVVASDMHNLDSRPPYMQQAYDIIAKKYGA KKAKELFVDNPRKIIMDQLI(SEQ ID NO 662)>orf00410MKEQNTLEIDVLQLSRALWKRKLVILLVAIITSSVAFAYSTFVIKPEFTSTTRIYVVNRDQGEKSGLTN QDLQAGSYLVKDYREIILSQDVLEEVVSDLKLDLTPKGLANKIKVTVPVDTRIVSVSVNDRVPEEASRIANSLREVA AQKIISITRVSDVTTLEEARPAISPSSPNIKRNTLIGFLAGVSGTSVIVFLLEFLNTRVKRPEDIENTLQMTLLGVV PNLSKLK(SEQ ID NO 663)>orf00413MDKKGLEIFLAVLQSIIVILLVYFLSFVRETELERSSMVILYLLHFFVFYFSSYGNKFFKRGYLVEFN STIRYIFFFAIAISVLNFFIAERFSISRRGMVYFLTLEGISLYLLNFLVKKYWKHVFFNPKNSKKILLLTVTENIE KVLDKLLESDELSWKLVAVSVLDKSDFQHDKIPVIEKEKIIEFATHEVVDEVFVDLPGESYDIGEIISKFETMGI DVTVNLNAFNKNLGRNKQIHEIVGLNVVTFSTNFYKTSHVISKRILDICGATIGLILFAIASLVLVPLIRKDGGP AI FAQTRIGKNGRHFTFYKFRSMRIDAEAIKEQLMDQNTMRGGMFKMDNDPRVTKIGRFIRKTSLDELPQFWNV FI⑶MSLVGTRPPTVDEYDQYTPEQKRRLSFKPGITGLWQVSGRSKITDFDDVVKLDVAYIDNWTIWKDIEILLK TVKVVFMRNGAK (SEQ ID NO 664)>orf00414VTFDKEDARSILENEIFYPCYYPTNRNLKNLIKNTILAFKILRKERPDIIVSSGAAVAVPFFYLGKIFG AKTVYIEVFDRIDAPTMTGKLVYPVTDRFIVQWEEMKKVYPKAINLGGIF(SEQ ID NO 665)[1793]>orf00415MIFVTVGTHEQQFNRLIKEVDRLKGEGFIQDDVFIQTGYSNYVPKFCKWEKVISYEKMNQLIKESDII ITHGGPATFMAVIAKGKNPIIVPRLKKFGEHVNDHQMQFVKITKEIYNLIVIDDISDLHLILHNFKDKHFETYLNN ERFNVRFNVEISNLFKGNKINEN(SEQ ID NO 666)>orf00416MKIRIEPQYFLYKYLWFIILLPKQFMQLILFFLIALTLLPTYIKEKQVFKIDTPSFCMVLWTIIYSISI IFNSLIDGLAVQVIFSDLSKAFNWLIAVFFYNYYLKMPINIDRIKRYMYYNFTILVVFVGLFYIQRGSNVILFGRSL LDWDGFTLATSYGVRYTGFLEYATLNGQLILFLLPLIRLFRFRFFTQTIIFAFLLEVLVLSKSRIAIVAMLIYIAFA VVNEINSNNKWLIGIFCPIIPFMLFYNFEKIKQIFFQMFSSRSGSNATRFRVYEESLKAINGMEMLLGAGVRIPSTV DILLGSHSMYISFIYRTGVLGSIIITVMFYYLFSKFLKCDSSERLRSIGYILALSVFWLFEELDPHYWCLILFFSTI SIFINNRKEEIVG (SEQ ID NO 667)>orf00417MIEVSIIIPIYNAEKTIKNCVDSALKQNLESLEVILVNDGSNDSTSKILEQY⑶NPQVMIFHQVNMGVS AARNVGLSYASGEYVFFLDSDDILDEGMLSKMYQFAKSNKIDLLSCWHKEPSTTQYGGNDNSSASFIARTKEEIGNH FVDIFPRSACAKLFLRRRIEENNIAFSTEMSLGEDMSFVCQYLMVSRSIAVIDGLYYTIQNVNPQSLSKRYVSNIEN SLLMQNQLWDQLLEVYPKIEENYYKQHMDFRFYLASLYVNNLFKFDSPYSSKEKWDNIAQQLKKYRPFLDEKVSKEK KPKNMNEMVIFYLLKSKIPALIYSFYSFKEWWKKKRLKN(SEQ ID NO 668)>orf00418MEDLVSIWPVYNVEKYLKKSIESILNQTYDNLEVLLVDDGSTDSSGEICDSFIKVDSRIRVFHKENG GLSDARNFGIEHMKGQYVSFID⑶DYISKDYVWKLYHSLKNNNSEVSICSFSLVDETGEKIKDELLDSGEVSLSGQ QILEKALTADGYRYVVAWNKLYRSTLFEKLKFKKGMLYEDEFLNYPLFWDCKRVSIVEEPLYLYVQRKGSIIQSN MTLEKIKMKDKMHTSRIEFYAEKKNSFLHQRSCQQYCNWIVTITVSHYNVLNVAFLKYLQHQFRRIVKYTQNDDK KLIIQNILGYINIRLAAYVKSKVM (SEQ ID NO 669)>orf00419MFPIYIISNQNIAFQQEIDIAYRKMKRQFSHISLTESEQKNDMNISNKVWICWFQGEERPPELIRTCIQ SMRTHFLGREIIVLTEENISDYIDIPDYITDKYKKGSISRAHYSDILRVELLCRYGGLWVDVTVLNTGGDFSNLELP LFVYKSLDLSRKDSQAIVASSWLISSYSNHPILLYARKLLWEYWRRKNSLCNYFLFHIFFTIATELYPIEffSAVLTF NNHSPHMFNFELNNQFSEKRWEQLKQISVFHKLNHHIDYSIGVNNFYKFIVFSKVEKNE(SEQ ID NO 670)>orf00420MSNKISKNLAYNIGYQLIGIAFPLITSPYLSRILGAENLGIHSFTISVALYFMMFMLLGIANYGNRTIA TVKREGKEILSKTFWNIYYVQLLMSVLVTIAYLIYLYFWVSSYKFIAILQLFLLLSNAVDITWLFYGLEDFKQIVFR NTLVKLLGLFLIFSFVHESSDLWKYTLINGGVTLVGQLLLWGQLKGRLSWVKIQKKDLLSHIKPILVLFIPVLAISI FSNMDKYMLGLMVGVKQVGFYDNANRIIDIPKALIAALEAVMLPRTSYLLAEGQEEKSNYYIEVTILYAMMISSVLI FGIISVSDIFSLVFWGEEFLESGRLIAAMAPVFVFSVPGNIIRTQYLIPRAKDKDYVLSLIIGALVNILLNCFLIKP FGAMGATISTVLAEFVLYGVQFWTVRRDLDFKKYLKNGFIFYLFGMIMYLAIIAVKAHLQYNIINLVLLIVLGGIVY TGFCCFYILISRNVHFEILREKIKRKIGYENIL (SEQ ID NO 671)>orf00422MFVADIMISDYSSAPIDFLLLNRVVFLYLPDFKEYQSDKNPFFEVFKVSKTKGIALDPFDEIIGRFQFG VRIV (SEQ ID NO 672)[1807]>orf00428MGFSMKLIHDLNTHTTHSTAKMLYNVKAIKNDFSIRE (SEQ ID NO 674)>orf00431MEQLHFITKLLDIKDTNTQIIDVVNRDSHKEIIAKLDYDAPSCPECGSQMKKYDFQKPSKIPYLETTG MPTRILLRKRRFKCYHCSKMMVAETPLVKKNHQIPRIINQKIAQKLIEKISMTDIAHQLSISTSTVIRKLNDFHFE CNFRNLPKIMSWDVETVRGVTVSIGRWR(SEQ ID NO 675)>orf00444LQIAQESSQDTDGINPPVVEEAMVFDRNDCLNQICGNIISLGIDAAFRTQVSNELIFIVVDFTRSCCN (SEQ IDNO 677)>orf00446MLNLMWMKIFHRNRTFLFCFLDFKVDVISIINARIVRR (SEQ ID NO 678)>orf00447MYNSQALRQIVVVGSIDHLFKRHSSICEIFGLRKRCLSFL (SEQ ID NO 679)>orf00472MSLADLLEELEAAKDSKKARSMEAYMRHQFSFLGIAVPERNKLYKNIFQKRKKQRLSIGILQTLAGKRS LENTNMWLLTI (SEQ ID NO 680)>orf00473MEKILLHNLNQTEFFINKAIGWTLRDYSKTNPTWVTCFIEKNKERMAELSIKEASKYL(SEQ ID NO: 681)>orf00477LSTCWNGKFCHICVALFHCFRAFKLALNEILCLLTNVSFIFVSVAF(SEQ ID NO 682)>orf00487LLGSFFSWTTKELMGIIFFNNFPTVHKNNMMGYISSKTYLIKLIKNSI(SEQ ID NO 683)>orf00509LKNVFSVGCHFFQFFVRFFWFGKFDHFNLVELVQTDQATRITTGRTSLRTE(SEQ ID NO 684)>orf00535LIDIKHFFLCLPLSKKMIIDIIVNKNPDRFCMIEKVKKTMAENR(SEQ ID NO 685)>orf00539VNIDSSEFYISHITDGIFDSFLDSNRYLRNFYSVLKVEIDICCEFFVHVFKINATAE (SEQ ID NO: 686)>orf00540VNTLYLCSSDSNDFFKYTWGDNDFAKLFFNSHRMTSF (SEQ ID NO 687)>orf00550VKEEKKAIVLGADNAYMDKVETTIKSLCVHHYNLKFYVFNDDLPREWFQLMEKRLETLNSEIVNV (SEQ IDNO 688)>orf00551VSNEIKIIALKLSIFWGHNHFRLTGNWKIFYLCLKSGLA (SEQ ID NO 689)>orf00552MKRIQLNMNETKKYLVIKAIAQGKKTKKRACVELNLSERQINRLLLAYQQKGKEAFRHGHGNRNRKPKH
120AIPDEIKERVLKKYLSYETYKPNVLHFCELLAEEEGIKLSDTTVRKILYKKNILSPKSHRKTKKRVRKQAKLNLNQP LDNPILPTAKDFLEDPKKVHPSRPRKKFAGELIQMDASPHAWFGPETTNLHLAIDDASGNILGAYFDKQETLNAYYH VLEQILANHGIPLQMKTDKRTVFTYQASNSKKMEDDTYTQFGYACHQLGILLETTSIPQAKGRVERLNQTLQSRLPI ELERNNIHTLEDANTFLLSYIQTFNEQFGNKTKLSVFEEAPNPSERNLILARLAERVVDSGHHIRFQNRYYMPVEQG KEVYFIRKTKALVLKAFDGDIYLNIADKIYHTKELLDHELYSKNFEQEPEQKKKDASISLHKPIRGNSHLSNNTFIK IKRIMKSLLVRSFILLNYKYNLFFAKWEAFP (SEQ ID NO 690)>orf00556LVEQLTFNQWVTGSSPVRVIYAGLAELADAPDLGSGA (SEQ ID NO 691)>orf00557MGEEEMRNKMIIAVSLVVAGVMTYLMFSGLDEDFYHFP (SEQ ID NO 692)>orf00567MNTIERTRRLVKGCATHCFEVVDRTDEVSSKHVFEVVDETNEVSSKHVFEVVDETDEVSNHTYGKAT (SEQ ID NO 693)>orf00581MLSNDFIQLRKDDIKTTSVLYFPIRLFSLETMNMSSQYF (SEQ ID NO 694)>orf00582LTCYPNPQKRLEAGFDKLIEIKRLTASKIQDILSVAPRSIGTTSPAREFE11ENIKHYKRLIDKAKK CVNDLMAEFNSVITTVTGIENRLGAVILAEIRNIHAFDNPAQLQAFAGLDSSIYQSGQIDLAGRMVKRGSPHLR (SEQ ID NO 695)>orf00595MKRIQLNMNETKKYLVIKAIAQGKKTKKRACVELNLSERQINRLLLAYQQKGKEAFRHGNRNRKPKHAI PDEIKERILKKYLSYETYKPNVLHFCELLAEEEGIKLSDTTVRKILYKKNILSPKSHRKTKKRVRKQAKLNLNQPLD NPILPTAKDFLEDPKKVHPSRPRKKFSGELIQMDASPHAWFGPETTNLHLAIDDASGNILGAYFDKQETLNAYYHVL EQILANHGIPLQMKTDKRTVFTYQASNSKKMEDDTYTQFGYACHQLGILLETTSIPQAKGRVERLNQTLQSRLPIEL ERNNIHTLEDANTFLLSYIQTFNEQFGNKTKLSVFEEAPNPSERNLILARLAERVVDSGHHIRFQNRYYMPVEQGKE VYFIRKTKALVLKAFDGDIYLNIADKIYHTKELLDHELYSKNFEQEPEQKKERRKYIPPQTHPWKLTSFKQYLHKNK KDYEEFTSEEIHSPQLQV(SEQ ID NO 696)>orf00601MDTKSSCLITTGRNDSPSTCLPRVASNNDRFSSEFRIIPDFHCSKKGIHVNMDDFS(SEQ ID NO: 697)>orf00604MMSIREQDLKDIGAIIKYKNFHSPFDTFKYLKDMGFDTIDLSVLLEGFSYAYGMDWLEKFFKENQDKLR EFY (SEQ ID NO 698)>orf00610MIPLYRTDNDITKFFTKIRNGHLAKTAGGLDDKFHEANASTSKAFDRQGVGEVNDIRDSAGSQELRIND KRKTENILFLEIRVRIFRVPHPNDSFFSSHFLG(SEQ ID NO 699)>orf00611VLSQGDKDITILDAGLLKNGKIGPVTKDTNDIKATD匪IENSFVLLNQQNIMLFCNQGATEGKTNFSPS DKDNFHNKTYFFMM (SEQ ID NO 700)[1859]>orf00616MKIKEQTRKLAAGCSKQCFEIVDRTDEVSSKHGFEVVDETDEVSNHTYGKAKLTWFEEIFEEYKMMGKA GQLVFFDVYRLVRQVS (SEQ ID NO :701)>orf00645LVEIVRGGSPRPIKDYLTSEVDGINWIKIGDTEKGEKYINNVKEKIKKSGLNKTRFVKKGTFLLTNSMS FGRPYILNVDGAIHDGWLAISNYENSLNKDYLFYILSSNVVYSQFLSLISGAVVKNLNSDKVASILIPLPPLAEQQR IIEAIESALEKVDEYAESYNRLEQLDKEFPDKLKKSILQYAMQGKLVEQDPNDESVEVLLEKIRAEKQKLFEEGKIK KKDLDISIVSQ⑶DNSYYEEVPCEIPESWEWVRLNDITSYIQRGKSPKYSNIPIYPVIAQKCNQWSGFSIDLARFID PETVHSYQKERLLRD⑶LMWNSTGLGTLGRLAIYHENKNPYVWAVADSHVTVIRVLSGVINCHFIYNFLSSPIVQSV IEEKASGSTKQKELLTKTIKEYLIPLPPLPEQSRIVDKIEQFFAHIDALI (SEQ ID NO 702)>orf00657MTPEQLKASILQRAMEGKLVPQNPNDEPASELLKRIKAEKEKLISEGKIKRDKKETEIFRGDDGKHYGK FADGSTQEIDVPYDIPDTWEWVRFSTLVEIVRGGSPRPIKDYLTSEVDGINWIKIGDTEKGEKYINNVKEKIKKSGL NKTRFVKKGTFLLTNSMSFGRPYILNVDGAIHDGWLAISNYENSLNKDYLFYILSSNVVYSQFLSLISGAVVKNLNS DKVASILIPLPPLAEQQRIIEAIESALEKVDEYAESYNRLEQLDKEFPDKLKKSILQYAMQGKLVEQDPNDESVEVL LEKIRAEKQKLFEEGKIKKKDLDISIVSQ⑶DNSYYGNIPMNWVVIKIKDIFSINTGLSYKKGDLSINKGVRIIRGG NIKPLEFSLLDNDYYIDTQFISSEQVYLKHNQLITPVSTSIEHIGKFARIDKDYDGVVAGGFIFQLTPFESSEIISK FLLFNLSSPLFYKQLKAITKLSGQALYNIPKTTLSELLIPLAPFEEQELITQKVEKLFEKVNQLWK(SEQ ID NO 703)>orf00669MCKANSRNDIFILQDSFCFEIFSRKKFKIVKEVLPNSTCKFRVVQ(SEQ ID NO :704)>orf00673VDRTDEVSSKHCFEVVDRTDEVSNHTHDKPTLTWFEEIFEEYHSPFHN(SEQ ID NO 705)>orf00674LDNIHIVLDSLNAVSGIQDFICDGLAIFCNQITSGCSSCK(SEQ ID NO 706)>orf00683MGPLLMHLCQQLVWLAKYLKRAGSDMMFLQEFLNRRFNPSLLGKIIL(SEQ ID NO 707)>orf00684LVAKGQGHKLRVSRHKDNQGIGVLFPNLSSHFQPLHLLISNLNIQKE(SEQ ID NO 708)>orf00692MTSYKRTFVPQIDARDCGVAALASIAKFYGSDFSLAHLRELAKTNKEGTTALGIVKAADEMGFETRPVQ ADKTLFDMSDVPYPFIVHVNKEGKLQHYYWYQTKKDYLII⑶PDPSVKITKMSKERFFSEWTGVAIFLAPKPSYQP HKDKKNGLLSFLPLIFKQKSLIAYIVLSSLLVTIINIGGSYYLQGILDEYIPNQMKSTLGIISVGLVITYILQQVMS FSRDYLLTVLSQRLSIDVILSYIRHIFELPMSFFATRRTGEIISRFTDANSIIDALASTILSLFLDVSILILVGGVL LAQNPNLFLLSLLSIPIYMFIIFSFMKPFEKMNHDVMQSNSMVSSAIIEDINGIETIKSLTSEENRYQNIDSEFVDY LEKSFKLSKYSILQTSLKQGTKLVLNILILWFGAQLVMSSKISIGQLITFNTLFSYFTTPMENIINLQTKLQSAKVA NNRLNEVYLVESEFQAPENPVHSHFLMGDIEFDDLSYKYGFGRDTLTDINLTIKQGDKVSLVGVSGSGKTTLAKMIV NFFEPYKGHISINHQDIKNIDKKVLRRHINYLPQQAYIFNGSILENLTLGGNHMISQEDILKACELAEIRQDIERMP MGYQTQLSDGAGLSGGQKQRIALARALLTKAPVLILDEATSGLDVLTEKKVIDNLISLTDKTILFVAHRLSIAERTNRVIVLDQGKIIEVGSHQELMQAQGFYHHLFNK(SEQ ID NO 709)>orf00699LRIYLHEPLITTVSQDFSSLSDISATHFEQLHIVAIVHSDIQRNNSPLTCDNRLSLHSVKFLFTRIIG (SEQ ID NO 710)>orf00723MGLIKTLAKIYGNYFLTVQGVKVMKTIKKDDNAVVGLGKLFIADKLMDTARffLIKPEDKK(SEQ ID NO 711)>orf00724MKFFWGLLAILFIKPIIGIVKFFWMIISFAVQLLFYKILDWFFKLI(SEQ ID NO 712)>orf00725MKIKEQTRKLAADCSKQCFEVVDRTDEVSSKHRFEVVDRTDEVSNHTYSKVKLTWFEEIFEEYKMILLL ILYHMERD (SEQ ID NO 713)>orf00733MHSQTFQFLLMTDKTSLLHRKHRSFIRNIHSKFLILFDLLCGILSRNDSNHNPIS(SEQ ID NO: 714)>orf00736MARTELPDKIETERLVLRVRTVADAEDIFDYASLPEVAYPAGFPPVKTLEDEIYYLEYIFPERNQKENL PAGYGIVVKGTDKIVGSVDFNHRHEDDVLEIGYTLHPDYWGRGYVPEAARALIDLAFKDLGLHKIELTCFGYNLQSK RVAEKLDFTLEARIRDRKDAQGNCCDDLRYALLKSEWEVI (SEQ ID NO 715)>orf00741MGKIVAIDLFNGAGGTTSGLKKSGIDVQVAVEIDSVAVKTYKLNNPEVSVIDME(SEQ ID NO 716)>orf00746LLRKQEGEYLRAENAILKKLRELRLKEEKEKEERQKLFKN(SEQ ID NO 717)>orf00768LKHLFCHFNPLWIDEIIRLAYKDQDTKDVKSKVKIGN (SEQ ID NO 718)>orf00792LCCNRHIANLDLEFISYYLGQVGFDTRISTGLGIFVTKIGNVLFDTDNQFASFLNVCDTSISLDWFGSS KAEKANQ (SEQ ID NO 719)>orf00817MKTKEQTRKLASGCSKHCFEVVDGTDVVSSKHCFEVVDRTDEVSNHTHGKATLTWFEEIFEEY (SEQID NO 720)>orf00819MDFFFMNEVKEQVLFRDNHSEHIFWIEGVSDFMIKVNTALW (SEQ ID NO 721)>orf00839MEELVTLDCLFIDGTKIEANANKYSFVWKKTTEKFSAKLQEQIQVYFQEEITPLLIKYAMFDKKQKRG YKQSAKNLANWHYNDKEDSYIHPDGWCYRFHHIKYQKTQTDFQQEIKVYYADEPESAPQKGLYMNERYQNLKAKEC QALLSPQDRQIFAQRKIDVEPVFGQIKACLGYKRCNLRGKRQVRIDMGLVLMANNLLKHSEMK (SEQ ID NO 722)>orf00840[1904]MHIHYNTNQTTLPLEISSFLPQDHLVFTIEKVVNTLEERHFYAFYHAFGRPSYHPKMLVSTLLFAYSQG IFSGRKIEKffKS (SEQ ID NO 723)>orf00843 LRLWVIFVMKVIKSYNTLNDYYRKLFGEKTFKVPIDAGFDCPNRDGTVAHGGCTFCTVSGS ⑶ TIVAP DPPIREQFYKEIDFMHRKWPDVQKYLVYFQNFTNTHEKVEVIRERYEQAINEPGVVGINIGTRPDCLPDETIEYLAE LSECMHVTFELGLQTTYEATSDLINRAHSYEL(SEQ ID NO 724)>orf00845VETVKRLRKYPKIEIVSHLINGLPGETHEMMVENVRRCVTDNDIQGIKLHLLHLMTNTRMQRDYHEGRL QLMSQDEYVRVICDQLEIIPKHIVIHRITCDAPRDMLLGPMWSLKKWEVLNSIEMEMRRRGSVQG (SEQ ID NO: 725)>orf00853MKIKEQTRKLAAGCSKHCFEVVDKTDEVSHIHTVRRR (SEQ ID NO 726)>orf00859VQVCVFTNFCFFHCFSSLANCRLFNLRGICLPCISYQ (SEQ ID NO 727)>orf00868VFKKDRFSIRKIKGVVGSVFLGSLLMAPSVVDAATYHYVNKEIISQEAKDLIQTGKPDRNEVVYGLVYQ KDQLPQTGTEASVLTAFGLLTVGSLLLIYKRKKIASVFLVGAMGLVVLPSAEAVDPVATLALASREGVVEMDGYRYV GYLS⑶ILKTLGLDTVLEETSAKPGEVTVVEVETPQSTTNQEQARTENQVVETEEAPKEEAPKTEESPKEEPKSEVK PTDDTLPKVEEGKEDSAEPAPVEEVGGEVESKSEEKVAVKPESQPSDKPAEESKVEQAGEPVAPREDEKAPVEPEKQ PEAPEEEKAVEETPKQEDTQPEVVETKDEAANQPVEEPKVETPAVEKQTEPTEEPKVEQVGEPVEPREDEKAPVSPE KQPEAPEEEKTAEETPKQEDKIKGIGTKEPVDKSELNNQIDKASSVSPTDYSTASYNALGPVLETAKGVYASEPVKQ PEVNSETKAEKVAANTDAKQSEVNSETASLKTAISGLNTDKVELENQLKIAQGKTETDFSMESWTVLSTAKNKAQEV KDNGTATQEQINEAEKSLKTALADLSVDKTALGSAIDTATKKNKENYTNQTWAELETVLTAAKSVNTNESKQSEVNE AVEKLTATIEKLVELSEKPRLTLSIEKRDIDRKVTVTYTLENPANTQIKSITATLKKGEEVVKDFVLTEENLKTNHL TALFEKLDYYKEYTLSTDMVYNRGNDDETESISEELIQLNLKKLELKDIQTVSLMKFENGQESQVTHLSDKPTDLSK LYLKVTSSTSKDAVLAVSSIEEEIVENKKIFKIHADTPELWRKKDGSLSKGFDYYMERVIPHD⑶IYYDFKDLISA MTSNPTGTFILGRDISSRNVKPDGNGKSYIKGEFKGKLLGTNDNVRHSIFDLEYPLFDTIKSGVVKDIDFKHVNMVF PDSNQ⑶NVATIARVIKDKTKIENVNVEGYLEGRDHVAGLVNNLEGNSEIENISFTGKIKSKGGNSITAGIAGRNIL SRVKRAYVNANIEVLGSTNSSMLVAVNGTTLNASGGWGAWGRLTESVAKGTLEIKRSGQAGGVTATVWPYGAIDKVV SYAKVTKGKELFGSDGDLNNNWFMQKINNIFGVQGISS⑶SGNDSKFKRISEEEAKQKVASYNITAPNLMSDSSLLV DRLNESWKNTDQFESIQDYQSQNQLIYQNLTKFTPYYNKEFIVHEGNALTPEQEILKTKKIKSIVGLKGTEFVVDGS DIDTIMLHFEDGSQKRYKVTSTGKFSITNLPEYQVEDLNVVYTSEHIVHPLDSSLINNLVEELKKVELYTESTYQVL GIDKDNANKLNRTKRLFLDESLDAVKTQLPTFVKTMFENEWLHINGESSGAVAALRQKIMDNKTAILLALTYINRYY DVKFSDYNIKKLMLFKPTFHGEKIDLLDRLIRLGSSGENRLKGSENAETFKQLFASETKQKDLVTYLDYNRSLLTNY QTTGEWFKETTKDYIQFEERPSLVEEIKDAKYRVYDNLTAPYYQGYILPLLTLKNTHLAILSNYSTMTFVSREKRPN WKNEDFDKWVKYVATAHRNHVDTffYKILPDNIKGKMVKENVTAVffEGLSIPGSEffVDQNAVDRKGRDYAPAREFFNL VGGPMGGffYAYHGYGAHAGGRNRVNYEVFDVLSEYGISVFTHELTHVNDTWIYLGGYGRRENMGPEAYAQGLFQSPV PGQPGWGALGLNMAFERKNDGDLIYNASPTQFENRKELDSYMKNYNDTLMMVDYLEGDAVISKGKEAITKWFKKVEP KVVSQTAQYDTVRQLTAEEKEKLSVSSVDDLVDQGLMSDRAVGNNTYNPADFETSYIAIDYMTGIYGGGKNSVGSPGALMFKHNTFRMffGYYGFEEGVLGYASNKFKQASRDEGHAGLSDNFIISKISKGEFLTMEAFKKGYFKKVVEELKT KGIRPVTINQKTYSTFEELQEGFKQAVERDLKKNQLDERETRNFKFQVFRQLLQQTDSFKTSIFR(SEQ ID NO 728)[1915]>orf00883VGNRIFIAFLQKLGLLDNLTGIREKLHPITGQGNTLGIADKDFNAHFIFQISHCIGETGLSDKELLGCL IHRASFDDFDNIM (SEQ ID NO 729)>orf00892MKTKKHRLLALALISSFTLLGAASAAVQYPDGGVWTYGEGSGGGWAFSNYYHGKKYHYSSLVSRWNSHS DKGEASAGKTSYAWIWTKWGEQVAFYCDYD (SEQ ID NO 730)>orf00903MSMIEVSHLSKSFGDKIALNDISFTVKEGQIFGFLGPSGSGKTTTINILTGQLLADKGQSIILGQKSQN LTSGELKRIGLVSDTSGFYEKMSLYNNLLFYSKFYNISKLRVDNLLKRVGLYDSCKMVAGKLSTGMRQRMLLARALI NKPAVLFLDEPTSGLDPTTSRTIHELILELKTAGTTIFLTTHDMNEATLLCDYVALLNKGKLVEQGAPSELIQRYNK DKKIKVTDYNGNQITFDFTSLEQVSQADLENIFSIHSCEPTLEDIFITLTGGKLNA (SEQ ID NO 731)>orf00911LISNKVDITLANFTVTDERKKQVDFALPYMKVSLGVVSPKTGLITDVKQLEGKTLIVTKG TTAETYFEKNHPEIKLQKYDQYSDSYQALLDGRGDAFSTDNTEVLAWALENKGFEVGITSL⑶PDTIAAAVQKGNQE LLDFINKDIEKLGKENFFHKAYEKTLHPTY⑶AAKADDLVVEGGH (SEQ ID NO 732)>orf00912MKLFKPLLTVLALAFALIFITACSSGGNAGSSSGKTTAKARTIDEIKKSGELRIAVF⑶KKPFGYVDND GSYQGYATILN (SEQ ID NO 733)>orf00946MTGKKGFLFLNCHICMVTTTTCFLKERVESELLIFFTFC (SEQ ID NO 734)>orf00948MDTPDENGYVADDYRITYLEAHIKAMRDAIYQDGVDLLGYTTWSCIDPVSAGTGEMNKRYGFIYVDRDN VGNGTLKRSKKKSFYffYMSFIAMV (SEQ ID NO 735)>orf00953LSCQIAFCLIDRLDYPIMFSKVCQENHFQVFTPFSKKLKNFLKNA (SEQ ID NO 736)>orf00966MFLGMIGNISIILQFFGITIIVKIDNQARAIDFFKHDKSSF (SEQ ID NO 737)>orf00968MFSLNFFDDNVFLSIKIAHKGCFQLLDMTNPNFFNKFFLAQASDQLLHFLSWNIEL(SEQ ID NO: 738)>orf00978MTEPDFWNDNIAAQKMSQELNELKNTYNTFHKMEELQDEVEILLDFLAEDESVHDELVAQLAELDKIM TSYEMTLLLSEPYDHNNAILEIHPGSGGTEAQDW⑶MLLRMYTRYGNAKGFKVEVLDYQA⑶EAGIKSVTLSFEGP NAYGLLKSEMGVHRLVRISPFDSAKRRHTSFTSVEVMPELDDTIEVEIREDDIKMDTFRSGGAGGQNVNKVSTGV RLTYIPTGIVVQSTVDRTQYGNRDRAMKMLQAKLYQMEQEKKAAEVDSLKGEKKEITffGSQIRSYVFTPYTMVKD HRTSFEVAQVDKVMD⑶LDGFIDAYLKWRIS (SEQ ID NO 739)>orf01011[1937]MQVIKRNGEIAEFNPDKIYQAILKAAQTVYVLTDDLRQNLAQVTKKVVLDLQEAKVERATISMIQSMVE HRLLGAGYITIAEHYISYRLQRDLERSGY⑶HIAVHLHFEQIR(SEQ ID NO :740)>orf01015MKIKEQTRKLAAGCSKHCFEVVDETDEVSSKHCFEVVDETDEVSNHTYGKAKLMRFEEIFEEY (SEQ ID NO 741)>orf01068 MKVINQTLLEKVIIERSRSSHKGDYGRLLL LGGTYPYGGAIIMAALAAVKSGAGLVTVGTDRENIPAL HSHLPEPMAFSLQDQQLLKEQLEKAEVVLLGPGLRDDASGENLVKQVFVNLSQNQILIVDGGALTILARTSLSFPS SQLILAPHQKEWEKLSGITIEKQKEDATASVLTSFPQGTILVEKGPATRIWEVGQSDYYQLQVGGPYQATGGM⑶T LAGMIAGFVGQFRQASLYERVAVATHLHSAIAQELSQENYVVLPTEISRYLPKIMKIICQQERGSKDKLV(SEQ ID NO 742)>orf01077VLDSKEELKESENDAPKLETPLREEPRLAPQTLPEASEVLENKREESKVEI IEPAQADDIRKVVGELA KDISITKLYMTGHSLGCYLAQIAAVEAYQKYPDFYNHVLRKVTTFSAPKVITSRTVffDAKNGF (SEQ ID NO 743)>orf01091LSYSILICLCNSTINESLRAFYCffQKFITFNQVTGNARGKGTTCTSIGPDN(SEQ ID NO :744)>orf01094MGRKPRTRPEERTELERLQAENEYLRAENAILKKLRELRLKEEKEKEERQKLFKN(SEQ ID NO: 745)>orf01096LSTCWNGKFCHICVALFHCFRAFKLALNEILCLLTNVSFIFVSVAF(SEQ ID NO :746)>orf01109 VVLSTSAILVACGKTDKEADAPTTFSYVYAVDPASLGYSIATRTSRTDVIGNVIDGLMENDKYGNVAPS QKDYDLNSTGWAPSYQDPASYLNIMDPKSGSAMKHLGITKGKDKDVVAKPGLDKYKKLLEDAVSEITDLEKRYEKYA KAQAWSTDSSLLMPTASSGGFPVVSNVVPFSKPYSQVGIKGEPYIFKGMKLQKDIVTTKEYNEVFKKffQKEKLESNS KYQKELEKYIK(SEQ ID NO : 747)>orf01113LNFDFFIFLAHFIPLFTFSILQENPKTSKKKLYIRLL (SEQ ID NO 748)>orf01119MGFSMKLIHDLNTHTTHSTAKMLYNVKAIKNDFSIRE (SEQ ID NO 749)>orf01134LIRIIRNIYRSGEGNTSVFQSFIDQINSNQFCYGSNFDRLRCILLIENFTSICLNSNRMFSGNGKILSN SSRSTP (SEQ ID NO 750)>orf01137MNATDIKNTYLKYIKENAVFNDVTDTHTEVITPFIDPLGEAIGFSIKSNGKHLTVTDDGYTIWNLSINN IDVTKKGRRQDIFNSLLHFNGFDLHDGAIERTTGKEHLGQVIHDMTQLLMNVYDFIQLTPNNIKSQFLDDVKSYFMK NEHYTVFPAFSIAGKSRLEHRFNFVFMSKGISKIARVHNNITKQQVDTILASWLDTSEYRRKEY⑶TEQLYIIVSDE GYNNIKDDHQIALQEYGINILNFSDKEQLEIQLGK (SEQ ID NO 751)[1960]>orf01138MSKVVKVTGAEVVISHNEEYLKVNPSELNFVPKLGDEVEVHKVDGEIIVIKVKDKKDDKININIVNEN NAMQNQSQVVHTQEIATGVHYVNKffVYVILALFLGGLGIHHFYAGYNGKGFLFLILSLTGIPAIIALFQGIIALFK KPDVYGRIAV (SEQ ID NO 752)>orf01149MKIKEQTRKLAAGCSKHCFEVVDRTDEVSSKHGFEVVDETDEVSSKHGFEVVDETDEVSNRTTVRRR (SEQ ID NO 753)>orf01156LQNDKNHKLFDNYTCQKEKDVLQCKQVKRKEERSYDVGTRIYTIYYFLLF(SEQ ID NO 754)>orf01158VDRTDEVSSKHGFEVVDETDEVSNHTYGKVKLTWFEEIFEEY (SEQ ID NO 755)>orf01159LFFKDEKQALYTKPKTKSSSFRASKVSNQTIVATTRTDCQVIALNLCDKLENGVVVVVQTTHHIGIDD VIYSKIFQHLTHSIKMSLAFFIKKVQDRRRILYCHLVFFFLRVQDTKRIFLQATLAILRQGLLERCQIVNQGLAVG CTALRISKSVEVQFDTLNTDFLQKMGCHSDCFHIGSWIARAKTLNTNLVELAQAPCLWTLITEHRSHIVELAWLL HFffGEEFIFHIGTDNGRSSFWTEG匪TVTLVIKIVHFLGYDIRCISDRATDNLVMLKNRRAHFCIVIALENLTGK ALNVLPLSRFSR (SEQ ID NO 756)>orf01164MEQIGKVFRQLRESRNISLRQATGGQFSPSMLSRFETGQSELSVEKFLFALENISASVEEILFLARGFQ YDTDSELRKEITDVLEPKNIAPLEDLYRREYQKHAHSHNKQKHILNAIMIKSYMKSIDERVELTAEEGKVLHDYLFS TEIWGIYELNLFSVSSPFLSVSLFTRYVREMVRKSDFLMEMSGNRNLFHTILLNGFLASIECEEFTNAYYFKRVIEE HFYKENETYFRIVYLWAEGLLDSKQGRVKEGQKKMEDAVCIFEMLGCNKSAEYYRNTTEC (SEQ ID NO 757)>orf01165LIPYFLHFIIFFRKFIKNLPNCQNYEKIEDIYHVEGLL (SEQ ID NO 758)>orf01167MKIKGQTRKLAAGCSKHCFEVMDRTDEVSSKYCFEVVDRTDEVSNHTYGKATLT(SEQ ID NO 759)>orf01170VVPFSDTFKDRNQVDIFTIKISRCNSSTIGENSWDIHISNSNHRSRHVLVTATDSDEGIHVVTTHSRLD GVRDDVTRC (SEQ ID NO 760)>orf01190MKKVKLGEVLSLKKGKKATVLAEQTTLSQRYIQIDDLRNNNNLKFTESL匪TEALPDDIL IAWDGANAGTVGYGLSGAVGSTITVLKKNERYKEKIISDYLGVFLESKSQYLRDHSTGATIPHLNKNILLDLQLELL GIEEQENIICILNTIKRLITKRKFQLDELNLLVKSRFNEMFEEYPDSVFLDTYIKELRAGKSLAGEENNKNKVLKTG AVSYDYFNSSEVKNLPIDYIPLDEHKVEI⑶VIISRMNTSELVGAAGYVWAINSDNIYLPDRLWKVILNDRVNPVFL WKLITNEKTKLKIKRISSGTSGSMKNISKSQLLQIRVPFPPLALQNEFADFVALVDKSQLAIQKSLEELETLKKSLM QEYFG (SEQ ID NO 761)>orf01199MKIKEQTRKLAAGCSKHCFEVVDKTDEVSSKHGFEVVDETDEVSNHTYGKATLTRIEEIFEEYKSS (SEQ ID NO 762)>orf01226[1982]MRLSIQLIHDLNTHTTHSTAKMLYNVKAIKNDFSIRE (SEQ ID NO 763)>orf01237 LVYAPFSFNILLDYITFDFKILLFSVFLAINRFHNDFIQFLL (SEQ ID NO 764)>orf01240LGTKIGISKNTIGNYEKRVKSTKKNTIFDLAKVFSSLIDALFPPVQKDSPSDIQSIYDQRAPPRQGKVL TYA (SEQ ID NO 765)>orf01246LFVFILIFLKSSIYIGIFWFIDFGKAVDFQGWKVLFEFFMVVIDQFSFGCNPGVVFILPGIALGQQSI DTRICDTVDNAESEQKLTIGMTGVVIDKACKLDCLALKFIWIVVDSLHDFHIVFISDLNTILG (SEQ ID NO 766)>orf01247MTVGFDLLHPDIQLNNCQDKGKHHGDIGQIGIVHVDVLV (SEQ ID NO 777)>orf01249MEGVAKGRIGRKKNNGIDNRCCHKKRNGRVTWNLFFQKTIDDGDDSTFTRREKYTDKGPKKDSPPTISR EKMINLVRCDINFNQP (SEQ ID NO 778)>orf01262VVIGVASATTNIffIIFLSGFTAILAGAFSMAGGEYVSVSTPKDTEEAAVSREKLLLDQDRELAKKSLYA AYIQNGEFKTSAQLLTNKIFLKNPLKALVEEKYGIEYEEFTNPWHAAISSFVAFFLRSLPPMLSVTIFPSDYRIPAT VLIVGVALLLTGYTSARLGKAPTKTAMIRNLAIGLLTMGVTFLLGQLFSI (SEQ ID NO 779)>orf01277MILMTKNINLTNEELELIQGGADPYGKEPNGYYPWKMEPVLTLLVHGFCPRDTDDLGYIGGGNHLCKGS AARF (SEQ ID NO 780)>orf01282LQVGQANEIGDPGAHFTQWNLLDDIGFDQLIQPNQKQYNDCHYCSFFHDFLF(SEQ ID NO 781)>orf01301LLHICIGETFDCIPYCMLTFFLSKSIGLTILLHKVKTVVFIDDQSNDKTCKICIHISFFRIKLSQQCQL SFSVYF (SEQ ID NO 782)>orf01309MTTIFLTRTSCSNCGKQSTFERFDRVYAAKTPEIISAILDWDFFKFTCHNCNHKVLIDYPTVVVDEEQK TIIQYCADGNVDVLSMQICSLISEGVNLSEYRIRVVSDIESFVEKVQIVSVGYDDRAIELMKYMNSPLEDGDIQFNY EHMVFTKVGHENYQFMFINNQIAVASLDFSQEQYEYYLADVEDLETNTYYIDSRWAESFFRTSLA (SEQ ID NO 783)>orf01310MVRRNSKITRQQKKIRDAFVSERTVEIIPAKREFTDVKTKKLRVAAYCRVSTFDESQSGSFELQKQTYT ERINSNPDWIMAGIYADQGASGTSIKRREQFQQMLHDCRCGKIDLIIVKSVSRFARNQLDFISIYRELKALSPPVGI YIEDINLNTLDTNSEFILGIMAIVAQGESEQKSASITWSVIERFKRGIPMIPTHNLLGYTKDQYGRVVIDETEAKIV RLIYDSYIEGMTASEIASTLMTNHIPTVTGLERWTSLAVYNILRNEKYKGEIIMQKTYTVDCFSHKTRKNNGEKPKY RLKNGIPSIIPESRWDLVQELLKQPRRKSKSTSEIFVPKLYIKKLKSGKLRDFVVLDPSWKSEDIHEVFK (SEQ ID NO 784)[2005]>orf01311MTVNKNFVTFSKGIVQALEYPAHVLVAFNKDTKVMGIQVCRAKTRGAFSFSKPVGEQKGIVQVGHKTLK ETLLTIMSEWKSDKRYRVEGIHIPEDKAFVFELKDFDELSDFRKNDNR(SEQ ID NO :785)>orf01313 MEKYNNWKLKFYTIWAGQAVSLITSAILQMAIIFYLTEKTGSAMVLSMASLLGFLPYAVFGPAIGVLVD RHDRKKIMIGADLIIAAAGSVLTIVAFYMELPVWMVMIVLFIRSIGTAFHTPALNAVTPLLVPEEQLTKCAGYSQSL QSISYIVSPAVAALLYSVWELNAIIAIDVLGAVIASITVAIVRIPKLGDRVQSLDPNFIREMQEGMAVLRQNKGLFA LLLVGTLYMFVYMPINALFPLISMDYFNGTPVHISITEISFASGMLIGGLLLGLFGNYQKRILLITASIFMMGISLT ISGLLPQSGFFIFVVCCAIMGLSVPFYSGVQTALFQEKIKPEYLGRVFSLTGSIMSLAMPIGLILSALFADRIGVNH WFLLSGTLIICIAIVCPMINEIRKLDLK(SEQ ID NO :786)>orf01315MELILKAKDISVEFKGHDVLDINELEVYDYDRIGLVGANGAGKSTLFKVLLGELIPPGCKMNHLGELAY IPQLDEVTLQEEKDFALVGKLGVEQLNIQTMSGGEETRLKIAQALSAQVHGILADEPTSHLDREGIDFLIGQLKYFT GALLVISHDRYFLDEIVDKIWELKDGKITEYWGNYSDYLRQKEEERKRQAAEYEQFIAERARLERAAEEKRKQARKI EQKAKGSSKKKSTEGGGRLAHQKSIGSKEKKMHNAAKSLENRIAALGKVEAPEGIRRIRFRQSKALELHNPYPIVGA EINKVFCiDKALFENASFQIPLGAKVALTGGNGTGKTTLIQMILNHEEGISISPKAKIGYFAQNGYKYNSNQNVMEFM QKDCDYNISEIRSVLASMGFKQNDIGKSLSVLSGGEIIKLLLAKMLMGRYNILIMDEPSNFLDI PSLEALEILMKE YTGTIVFITHDKRLLENVADVVYEIRDKKIKLKH (SEQ ID NO 787)>orf01316MNQLEFQRNHLQMDYYSESYQDFERDFYRYSNMNIPLTFLTDDILKTMATSRKNYFVLNKEKSRDNRDH FFIFEVRTLEENPLIYHYTYKKTTTYLAEK (SEQ ID NO 788)>orf01317MQKWMGFFLSEHTSALTDDANKVTYMSDLSLEKKLLLLSQVYAGQLNTRIHVVKKNNQVSYTGTIPSLT KDFILIKTTTGHINLKLKDIVSIELVEEVLYESA (SEQ ID NO 789)>orf01318MKKSINAQKKIDPANLPKTMVGHVLELFRKKYTSGAVRQIGVSYGGFVDENFTLLSLFDDVEQIEKENR LQTAIDVVREQFGFLAIQKGTVLTEGSRNIERSKLIGGHSAGGLEGLK(SEQ ID NO :790)>orf01343MNXXFISTKDKHTLIQVSAVRFRDGREIDAYDSYVHTSVPLKSFINEFDRGLQLRP(SEQ ID NO: 791)>orf01363MIAMRSYITLTCNLNNNLFCLNSFFLTNLVWSQIFSLLSVFITVYI (SEQ ID NO 792)>orf01364MVFDANRIISEDSEGFVIPHGDHNHYIKVQTKGYEAALKNKIPSLQSNYQPGTFDEKAVLAKVDQLLAD SRSIYKDRLS (SEQ ID NO 793)>orf01390MARLEPAKIAKIVLGILLYIIDLIKSSFVLPIPKAAKKSLILISFVPSFNDKNIVIRRPRQITKIMPRF ICFLFRIFACIS (SEQ ID NO 794)>orf01396[2026]MASKRLSIEEQIEKKEESIKQLQNQKRQLKKKLNEQERKARNKRLIEKGAVFESIFEESIDLTKDEFYK LIKTLNDEEIRLNIMEILEERIDDNVEKSSKDEIT (SEQ ID NO 795)>orf01397MADSFHFSVNIISRGKGKSAVASAAYISGEKIKNEWDGVTHDYTRKEKILVKNIILPDHIPKEFNDRST LWNKVEMAEKNSNAQLARQFIIGLPKELSLSENKNLVERYIKENLTSQGMIVDYAIHDESQDKNGNIHCHIMTIMRP INEKGEFLAKSKKEYILDEKGEKVLNKNGKPKTRKVELTTWNDTGNVEKWRENFSDLCNKYLERAGAEKRVDHRVLK DKIQIIYRQSI(SEQ ID NO :796)>orf01398MERKGIETDKGNYNREIRKYNQLVKTIKEEIKTLKGffIGNLLDNLSTAYEKFKDIERDKVIDNPKLFN LTNYLLTYSEIQKEKSKYLKGYAKTNKEKYDFKKLTSAYSYLRKNNIETIGQLQTKIETLKSNSYRLNKKAKTIHK EMEDVEKKILYYEIYKAKKEVYEEYQKKNIFTKEAFYNKHKKDIDQYKVVSGKLKKLLSDKEKLSPKKffNEEKIL LMSNLEEINKEKDKIKDEYQEINHIKYSVDFVNKELGIDLSIEIDKLIKQGEKPSVIAQIKKFQDQVNKDNEYRE MMKNKKMDQER (SEQ ID NO 797)>orf01407MELSAIYHRPESEYAYLYKDKKLHIRIRTKK⑶IESINLHYGDPFIFMEEFYQDTKEMVKITSGTLFDH WQVEVSVDFARIQYLFELRDTEGQNILYGDKGCVENSLENLHAIGNGFKLPYLHEIDACKVPDWVSNTVWYQIFPER FANGNALLNPEGTLDWDSSVTPKSDDFFG⑶LQGIIDHMDYLQDLGITGLYLCPIFESTSNHKYNTTDYFEIDRHFG DKETFRELVDQAHHRGMKVMLDAVFNHIGSQSLQWKNVVKNGEQSAYKDWFHIQQFPVTTEKLVNKRDLPYHVFGFE DYMPKLNTANPEVKNYLLKVATYWIEEFNIDAWRLDVANEIDHQFWKDFRKAVLAKNPDLYILGEVffHTSQHWLNGD EFHAVMNYPLSDSIKDYFLRGIKKTDQFIDEIN(SEQ ID NO 798)>orf01408MFNLLDSHDTERILWTANEDVQLVKSALAFFFLQKGTPCIYYGTELALTGGPDPDCRRCMPWERVSSD NDMLNFMKRLIKIRKYASVIISHGKYSLQEIKSDLVALEWKYEGRILKVIFNQSTEDYLLEKEAVALASNCQELENQLVISPDGFVIF (SEQ ID NO 799)>orf01414MSEQYRDIRKEVNLTADELKQIEKMMEVDNYRHFSPFVRDKILMTDDKQLAAKEWFSLWQSQKFEQISR DVHLVLIIARENHQVTQEHVSILLTCVQELIAEVNQVQSLSRGFREKYMR(SEQ ID NO 800)>orf01415MVYRYRTNLKKVFLTDSELHQLNERIAKSNCQNFSVYARKVLLNP匪SFVTINTDTYDQLVFELRRIGN NINQIARAINQSRLISQEQLQELSKGVGELIKEVDKEFQVEVKRLKEFHGSH (SEQ ID NO 801)>orf01417MVVTKHFATHGKKYRRRLIKYILNPDKTDNLKLVSDFGMSNYLDFPSYEEMVEMYNVNFTNNDKLYEY RNDRQEKHQQNIHAHHLIQSFSPEDNLTPEEINRIGYETIMELTGGRFRFIVATHTDKDHIHNHILINAIDCNSDK KLIWNYALERNLRMISDRISKMAGAKIIEKRFSYRDYQKYRATSHKFELKQRLYFLMQQSKSFDDFLEKAEQLHV HIDFSQKHSRFMMTDRAMTKPIRGRQLSKRDLYDEDFFRMHFTKQEIASRLEFLLNCVNSLEGLLTKSKELNLTI DLKQKNVIFIleengkqfslshkkIsdeklydVNFFQDYFKNKEVGVSEGIenlqaqyrafqeerdkekvsteeI EEAFETFKEKRDAVHEFEVKLTEHQIEKLVDEGIYIKVSFGINQSGLIFIPNYQLDIMEEENQKKYKVYIRETTS YFVYNKEHSDKNQYIKGRTLIRQLTNDSRVIPYRRPTVERLQEKISEISLLIELTETDKKYQDIKDNLVSEIAEL DIKLTQTNEKIATLNKMAEVLINSKSEGSGSQKLARHEFSKLNMTESTTLEQVNEELLKLQQEFGNVLDEYEKTIRKLGQLFKVFDECINKEIMNEI (SEQ ID NO 802)>orf01419MVCLIIDVSPYSTLCDIVVPKTHFLRQLMELCDFSFIYDELEKNYQPDFGCRSYSLLIMMFKYLLLKDI YKLSDVDVVERSFSGMTFKYFLGLAPVIEPSSLTKFRKLRNKDERLLDLLIAKSVQIAIELGLIKSNILIVDATHTK VHYNHKKPQEVLRERSKALRKTIYQYSEYIKAEFPSKPQEDTLVAELRYTQEVISVLEKHDELTGIPAISQNSITLK KL (SEQ ID NO 803)>orf01420LESSVKEEARIGHKSADSSFYGYKEHFAMTDERIITACVVTSGEKSDGPVLEELYHKSKDNGVTIEAIV GDRAYSGKD匪QFTKKERVH (SEQ ID NO 804)>orf01421MSVFKFRIFGFYLVAMFGLFFKIGRFLKPLLENMFIALKGYQISLRLSPFFITAHF(SEQ ID NO: 805)>orf01425MQEHYTPKGKHLTIDNRRLIERWKNENKSNREIAGLLGKAPQTIHNEVKRGTTLQQVRKGLYKKVYSA DYAQTVYQFNRKRSVKKLILTKEIREKILHYHKQKFSPEMMVNKKQVKVGISTIYYffFHNGHLGLTKADMLYPRKR KGVKKQASPNFKPAGKSIEERPDVINLRLENGHYEIDTVLLTKIKNYCLLVLTDRRSRHQIIRLIPNKTAESVNQ ALTLLLGEHRILSITADNGSEFKRLSEVFPEEHIYYAHAYSSWERGSNENHNRLIRRffLPKGTKKTTPKEVAFIE NWINNYPKKCLDYKSPSEFLLGG (SEQ ID NO 806)>orf01426MLHPIFIIRRSWDGIFHLSEWKRNEEFDFFNKMDVPYLSMSSRIEVTQAINFHKKHSISLYAIISffCVM SAINSIPELLMDTDGKIVWQYNQRGCSFTTLTSEDKLNFSSFTMGDNLIEFVSAFNINKQKAEEGQKPNIDKNNIAY LSCVPWIDFLHVSTPMNLSKIDTVPRITWGKVIQENQRYFCTVNLQINHGMGDGLHVSNFFVLLQRFVNKINEYFQK K (SEQ ID NO 807)>orf01428MSIFIGGAWPYANGSLHIGHAAALLPGDILARYYRQKGEEVLYVSGSDCNGTPISIRAKKENKSVKEIA DFYHKEFKETFEKLGFTYDLYSRTDSPLHHEIVQELFLQLYEKKFLYTKKIKQLYCTFDNQFLPDRFVEGKCPNCGT HSRGDQCDNCSAILDPIDLVDKRCSICSNEPEVRETEHFYYVFSEFQNLLETYLNDAEETVRWRKNAINLTKRYLRE GLPDRAVTRDLPNGIPVPIDGFRDKKIYVWFEAVAGYYTASVDWAQKLQNNITDFWNNRTKSYYVHGKDNIPFHTII WPAILSGLEIEPLPEYIISSEYLTLENKKISTSNNWAIWLNDIIKKYDADSIRYFLTINAPEMKDANFSffREFIYSH NSELLGSYGNFINRTLKFIEKYFESEIPTKYLEGEILYNLKELYTTVGNLVESGHMKQALEEIFEYIRSANKFYDDM KPWALRESDIEKCKEVLATCVIIILNLGQMLNPFIPFSGKKIEDMFKTKLNTWNYISNLPNKLSDVSMLFDRIDLKK IDEEVLELQQTSSR(SEQ ID NO 808)>orf01429LNNLTLLKEYNFRDLGNHLTQTGQKIKPKTLFRSSKLFGISKIDVDLLQSYGITKVIDFRSANEIKKAP DPDIKNIKNIVIPIFYNDDSELTEFPIEFFNKSDAGFQHMIKTYDQMINQKQSKLGYKKFFKLLLSHPKDESLLFHC SMGKDRTGIASLFLLYILGVDMNDIFHDYLLSNKYLINVRKENIEYVNNHSGNVILMHNLLSLSSAKEEYINRVLNVLDKEYGGILRYINTELGISSQEIEELKDRYLF (SEQ ID NO 809)>orf01431MDFLNEVLDLKEFIQDPVRTLSLGQRMRADIAASLLHNPKVLFLDEPTIGLDVSVKDNIRRAITQINQEeettilltthdl⑶ieqlcdrifmidkgreifdgtvnqlkktfgkmktlsfelhpgqdyivshfeglsdiyvtrqel sldiqydssqyqtadiiqqtlsdftirdlkmtdaniediirrfyrkel (seq id no 810)>orf01432 mtklwkrykpfvsagiqelityrvnfflyri⑶vmgafvafylwkavfdsshqsliqgftlsdmtlyii msfvtnlltksdssfmigwevkdgsiimrllrpvhfamsylfteigsrwlvfvsvglpfviliaglkllsgesflqi vlittvyllslilaflinffsifalvfqllclkty⑶qif (seq id no 811)>orf01433mkkyqrmhlifirqylkqimeykadflvgwgvfltqgl 匪 lflnilfqhiplldgwsfhqvafiygfs lipkgidhlffdnlwalgqhlirkgefdkyltrpisplfhilvetfqidalgellvgvllllmtitsltwtwakvfl flisipfatliytslkivtasiafwtkqsgaiiyifymfndfakypiaiyhsflrwlisfiipfaftayypasyflk dkdglfnigglilislifftlslklwnkgldayesags (seq id no 812)>orf01434mielaeplpeyeillsipgiaettatsiigeletfvafslptksmplsvltsdtmnlais(seq id no 813)>orf01435MLGffKDGHEVPILFPCRSREKVLYFWKGNLKHLVQAILSPNDVFCQILIESTEVTQILIDFFLNISWFA vkdel (seq id no 814)>orf01437mmrtvfrmdvskassevailvngekvhgytmpndaigfsrlledlk(seq id no 815)>orf01438mkknnveiikadslvrrr⑶nverhlkrvaaycrvssdsedqknsydsqvrhykeyisqrsdweladiy adegisgtqvgkrqdfqrlindcangeidyivtkaiarfarntldtlkyvrmlkdmqigvyfeeenidtltmdgell ltilssvaqqeventsahvkkglkmkmqrgelvgfqgclgydydvetkqisinkkeakivryiferylegiggkvia reldelgyksprglehwndttvlgiiknekykgdilmgktftvdpiskrrlsnfgeedkyyikdnhepiiskedfek aqeirlrragnkktaanvngkreryskmyafssmlecgfcgsilsrrswhcrsdyrkvvwhcvtsikkgkkfckhsk gleeiaiegafleayrqvyhsnenlmtdlletieselndnslnkelkritnklrillkkeenlvnlrlegkvsdsiy nekyneissekeflaeekvniettlkseidvkkrltefkhllssqkmltefdravfesivekiivggvnsngeidpa mlt11fktgeiqnkdgkqfkskrknakletdklcpqnsdedkklysqgtdntrgvcsvagsilasq (seq id no 816)>orf01439mggnppmkkysivdkivlstkikriiiftvfrenwepymkkytevfqsqfpnlnidyllldteqidlds
yldadiiiigggntekyiatyvnqefksyidhmlnkeakiigfsagalllgekvyvspndnsdhqikiknglglfsq
flisvhydswndkankdraeelvnvpiiplndhsclvldklgniiekid (seq id no 817)>orf01440mddeaskqlsdsrfkilvgvqrttfeemlavlktayqrkrakggrktklslddllmvtiqymre (seq id no 818)>orf01457mgfsmklihdldthtthstakmlynvkaikndfsire (seq id no 819)>orf01492[2076]LILNEYEKRIFHEKTHNIECFDTCYYAFFIIFAPFLAFVIDKHCSSSLFLER(SEQ ID NO 820)>orf01520MSQVKGLCVLDVDGTLILEEVIDLLGREAGHEAEISQITSRAMRGELVFESSLRKRVSLLEGLPILVFD NVFNSIHLSLNVPEFISILQKNGILVGLVPGGFTPIVGEISKIPWYCLFHCQPA(SEQ ID NO 821)>orf01521 MLKSAELGIAFCSKEMLKKEIPHHVDKRDFLEVLPLIDCLE (SEQ ID NO 822)>orf01527MGFSMKLIHDLNTHTTHSTAKMLYNVKAIKNDFSIRE (SEQ ID NO 823)>orf01537MDKLIIFIEKGKPFFEKLSRNIYLRAIKDGFISSMPAVLFSSIFILIAAVPNIFGFKWSDEQLAFILKP YNYSMGILALLVAGTTAKSLTDSVNTRSMEKTNQINYMSTFLAAVVGLLILAADPIEGGFANGLLGTRGLLTAFLAA FITVNIYKVCIKNNVTIRLPEEVPPNIAQVFKDVIPFALSVLSIYGLDLIVRNIFGTNVAESVGKILAPLFSATDGY IGLAIVFGAYAFFWFVGIHGPSVVEPLIVAISYANIEANVQLVQAGMHADKILNPVTQTFVVTMGGTGATLVVPFMF MWLCKSKRNRIVGRASVVPTFFGVNEPILFGAPIVLNPIFFIPFVTAPIINVWIMKFFVDVLQMNSFSIILPffTTPA PIGIVMGTALAPLSFVLAITLIIIDTLIYYPFVKVYDHQILEEERKGNSSSELKEKVAANFNTVKADAILEKAGVDA AQNTITEETNVLVLCAGGGTSGLLANALNKAAAEYNVPVKAAAGGYGAHREMLPEFDLVILAPQVASNFEDMKAETD KLGIKLAKTEGAQYIKLTRDGKGALAFVQEQFD (SEQ ID NO 824)>orf01552LFKTRSNSSALGSSYISNRNIFSYFTNQFNNTFCNVFGM (SEQ ID NO 825)>orf01557MALTQRQFVELFQETINVITLTCLTVSVAVVACVSICSS (SEQ ID NO 826)>orf01558MLTMFLFLPIDFFFCTDIIRMSCILKVNIVFSIYLNHITTLDFTDNILVL(SEQ ID NO 827)>orf01560LVCYFDDDLFGIDSFTLANLIRSQILRFLRRLFSIYIGNTIISLTVLA(SEQ ID NO 828)>orf01570MGFSMKLIHDLNTHTTHSTAKMLYNVKAIKNDFSIRE (SEQ ID NO 829)>orf01585MEKYFGEKQERFSFRKLSVGLVSATISSLFFMSVLASSSVDAQETAGVHYKYVADSELSSEEKKQLVYD IPTYVENDDETYYLVYKLNSQNQLAELPNTGSKNERQALVAGASLAALGILIFAVSKKKVKNKTVLHLVLVAGIGNG VLVSVHALENHLLLNYNTDYELTSGEKLPLPKEISGYTYIGYIKEGKTTSDFEVSNQEKSAATPTKQQKVDYNVTPN FVDHPSTVQAIQEQTPVSSTKPTEVQVVEKPFSTKLINPRKEEKQSSDSQEQLAEHKNLETKKEEKISPKEKTGVNT LNPQDEVLSGQLNKPELLYREETIETKIDFQEETQENPDLAEGTVRVKQEGKLGKKVEIVRIFSVNKEEVSREIVST STTAPSPRIVEKGTKKTQVIKEQPETGVEHKDVQSGAIVEPAIQPELPEAVVSDKGVPEVQPALSEAVVTDKGEPAV QPELSEAVVTDKGEPAVQPELSEAVVTDKGEPAVQPELPEAVVSDKGEPAVQPELPEAVVTDKGETEVQPESPDTVV SDKGEPKQVAPLPEYTGPQASAIVEPEQVAPLPEYTGVQAGSIVEPEKVEAPKEYTGKIEQPSAEDTKPENEASSTN GESERPKDKIKEEKQVDKKLELRNVSNVELYTVENNKYRHITAVDGALDSSLKYFMKVKSENFKDIMLPVTKIESTT KNNKEVYKIVAHAENLIQHENNVISNDYTYYLPKTQQSETGVYTSFKNLVDAMNSDPNGTFHLGATMDAREVELPDD QESYVKNEFYGKLIGENNGKYYAIYNLKKPLFKTLNTATIQNLSIKEANVSSKEDAATISKEAKYNTLIDNVHSDGIIAGERGIGGLVSKVDNSRISNSSFTGRITNTYDTTAGYEIGGLVGKLSGSLASIEKSIASIDIASNAKS⑶QIVGGI AGVVEKSATIKYSYVEGNVNNVRHFGKVGGVAGNLWDRDSQDVSKSGKLSYVLSDVNVTNGNAIAGYNFNGIKTIET YSNKNNKVVNVVQEDDEVVTKDSDVQRGTVLDADKVKEKKVELVSKHSTKVEDFDFTSRYNTNYNEVTGYQQSREQV YKNIEKLLPFYNRETIVKYGNLVEDNSDLFTKKLLSVVPMKNNEVITDINKNKQEINKLLLHFEGNKSRVLNIAYKN DFSKVAEYDIANTKLMYTPNTMLHDYNNIVKTILNDLKSVQYSSADVRKVLDISGNIKLTELYLGEQFEKTKANIED SLSKLLTADAAIVENNNKVIDNYVIEKIKNNKEALLLGLTYLERWYNFNYGETNAKDLIMYHLDFFGKSNSSALDNV IELGKSGFNNLLAKNNVITYNVLLAKNYGTESLFKALEGYRKVFLPTISNNEWFKKQTKAYIVEEKSTIEEGREKQG KEGTKYSIGVYDRLTNPSWKYQSMVLPLLTLPEEKTVFMIANISTIGFGAYDRYRSSEYPKGEKLNKFVEDNAKEAA KRFRDHYDYWYKILDNDNKEKLYRSILVYDAFKFGTDKDKDKVTHQATFETDHPAIKYFFGPAGNNVVHNGHGAYAT GDAFYYMAYRMLDKDGAVTYTHEMTHNSDREIYLGGYGRRSGLGPEFYAKGLLQAPDHPYDPTITINSVLKYEDSEN STRLQVADPTQRFNSAEDLHNYMHNMFDVIYMLEYLEGKAVANLETNQKYELLRKIENKFDLDQDGNNVYATNVVRR LTMDEVNKLNSFDSLIENDIITSRGYKDQEYKRNGYYTIDLFSPIYSALSGEKGTP⑶LMGRRIAFELLAAKGYKEG MVPYISNQYEKDAKAAGSKINSYGKEVGLVTDELVLEKVFNGQYKTWTQFKKDMYKEREKQFSKLNRVNFINPNNP LSRQRNVSVTDIGVLERMIVEAVRDDAQDDVAKFYPETNSRVLKLKKAIYKAYLDQTNDFRSSIFENKK(SEQ ID NO 830)>orf01588LSLLKKDKFSIRKIKGIVGSVFLGSLLFAPSVVGASTYHYLDYSSLTQTERDQLKQGRPDESKESYALD YEKDALPNTGSSQSIMTALGLLAIGSLIVIITKDNRNKKIATFLIVGATGLVTLSTASALNLNANIHESGRDGVLQI SGYRYVGYLELDDKTVSSVSPASTVSPVEQPKVVTEKGEPEVQPALPEAVVTDKGEPEVQPTLPEAVVTDKGEPEVH EKPDYTQPIGANLVEPEVHEKLAYTESVGTTGMDENGNLIEPPVSDIPEYTESVGTTGVDENGNLIEPPVSDIPEYT ESVGTTGVDENGNLIEPPVNDIPEYTEPISTVSEVASEREELPSLHTDIRTETIPKTTIEESDPSKFI⑶DSVKEVG EDGERQIVTSYEELHGKKISEPVETVTILKEMKPKILVKGTKENPKEKTVPVLTLTKVTEDAMNRSANLNYELDNKD NAEISSIIAEIKDGDTVVKKVDLSKEKLTDAVQNLDLFKDYKIATTMIYDRGQGSETSKLDEKTLRLELKKVEIKNI SSTNLVKVNDDGTEIPSDFMSEKPSDEDVKKMYLKITSRDNKVTRLAVDKIELVTEKEKELYKITASAQDLIQHVDP SKTRNEYIHYIEKPVPKVNNVYYNFNELVRDMQEHPNDEFKLGADLNATNVSAFGKSYVTKDFKGKLLSD⑶NHYTI HNLSRPLFGNVIGGTIKNINLGNVDINMPWANQVAAVANIIKGGTTIENVKVKGNIVGKDWVSGFIDKIDNQGTLRN VAFIGNVTSVGDGGQFLTGIVGENWKGLVERAYVNANLIGKKAKAAGIAYWTQNEGNNNTVRQEGAIKKSIAKGTIQ VTEAIESGGWGSMKHHGSVEDSVSMMKVPNGEIFYGSSDIDYDDGYrreDNVRRNYWIGVSDGHSSYQRSKDKNR IRPISEEEAKSKIEATGITADKYEINEPVVNRLNRLTRREDEYKSTQDYKVDRDLAYRNIEKLQPFYNKEWIVNQGN KLAEDSNLAKKEVLSVTGMKDGQFVTDLSDIDHVMIHYADKTKEIKAVHQKESKVAQVREYSIDGLDDIVYTP匪VD KNRDQLIKDIKDRLATVELISPEVRALMDKRDTSRDPNANSDERKNGYIRDLYFEESFSETKANLDKLVKSLIENAD HQLNSDEAAMKALVKKVDENKAKIVMALTYLNRYYDIKY⑶MTIKNLMMFKPDFYGKSVDLLDFLIRIGSSERNIKG DRTLDAYRDMIGGTIGKSELHGFLDY匪RLFTNDTDLNDWFIHAAKNVYIVEPKTTNPDFVNKRHRAFDGLNNGVHN RMILPLLTLKNAHMFLISTYNTMAYSSFEKYGKYTEAEREAFKDKIKEVAHAQQTYLDFWSRLALPSVRDQLLKSQN RVPTPVWDNQNYHNVEGVNRMGYDKNNKPIAPIRELYGPTWRYHTTNWYMGAMASIFQDPNNNDQVYFMGT匪ISPF GlSAFTHETTHVNDRMLYFGGHRHRQGTDVEAYAQGMLQTPDKSGNGEYGALGLNMAYHRENDGDQffYNYDPDKLKT REDIDRYMRNYNDALMMLDHLEADAVIPKLHGNISRWFKKMDRQYRKNGELHQFDKVRELTEDEKKKIVINNIDDLV NNNLMTKHGAPSDRTYNPEDFDSAYVNINMMTGIYGGNTSQGAPGAASFKHNTFRMWGYFGYENGFISYASSKYQGE ADKTNKKLLGDDFIIK KVSKDKFNNLEEWKKQYFKDVKSKAEKGFTAIEIDGRQITNYAQLKTLFAEAVQKDIDGMSDPKIKDHFKNTVDLKSKVFKALLKNTDGFFNKLFKEDI (SEQ ID NO 831)>orf01603VLGGRANSVTSCTTNSHWNLTFTTKHVTCFSSLVDDIVHGNNREVHEGHIDDWTKSCHGCSCCCSRDGS FRNRTVTDTFWTKFFKHSNRSTEVSSEDTDVFSHQEHIFIATHFLRHSKDNGVTEGHCFCFHFISFSLVCVNIFKG (SEQ ID NO 832)>orf01604MDMFYIGHFLDIRRDTVTVVNAIENDWQVPDRSHVHCFVENTFIGRTISKEADNDFTGILHLLTEGCTD SDPHTTTYDTIGTKVPSIKVSDMHRSTFPFTGSSVFTKDFSHHSVEVNPFSNSLPVSTVV (SEQ ID NO 833)>orf01606MNXXDFIGHCDKIKRNIFEKSHKVFSGLFGLHPKDFLNLIFSNQIPLPFSECNPLTNYNHLFSLIISDK RDIVIHWI (SEQ ID NO 834)>orf01622LIEIQVFSSLQVCCLNLCHLKFQHFDTCLVFLLVFLDFQNLLAHFPIGIKTRLIGFFQVPKSGITKFIQ HLDMQLGTH (SEQ ID NO 835)>orf01623MVMLTMNIYKMLPNSSQNRQINHLTIYTADTTTILQDFPTDDNFIT(SEQ ID NO 836)>orf01624MTNNICRRTSSQHHIHGINDNRLPCTRFTSQDSHPLFKIEGNSLNNGKVFYRNFK(SEQ ID NO: 837)>orf01634LFVIRNPSSQTLFQTQLQLVQALQITVIQALRLSKDNRLTAFFQSLLFLR(SEQ ID NO 838)>orf01636MPHTRDNWQTRFKNSSYHNFFVKGPEILNRTTSTTNNEQIQIVPLISTRNISSNFLRSPFTLNLGRIK KDVNTffESPADGRDNISNNGSTTAGYYPNSLRKLGQSLLEAFLKQAFFCQFFLKLFKLNRKRPNPIRLNFFNDDGV ATTffFIDLYTPNHIDLHSFFQVKP(SEQ ID NO 839)>orf01637VTLADFVADRRAATPTAAAELATPVTKVGCISSFAKSGKTDGNGSPKCSI(SEQ ID NO 840)>orf01640LAIIRNRTCSLKLINDHLTFWTLRFLTSTRILIELATINLNCRIHRGNLSNRPSQASNRFINKLFIQG RQNRGFCDHFPTSILSRRGIAQSDFPLIDLTLVLHKLDHACRLANRNRQNTHHIRIQGSTMTNFLGSQNLTQFKNR IMRGHSCFLF (SEQ ID NO 841)>orf01642MEDDLNYENLMDDVTEAIKKFNLVIFIGAGVSIAQGYPNWNNYIEHLIKYWQGQVLSVSGEKRLGREHH VVFDLISKSSISNKRKVDLVNYELKKVFGEDFEKRRLDFEKGYFKNLLPYSIVNQTVESLASLNAIFITSNYDYEIE NHIKRLKNAVVTINDLNEFTKNKNGKLQF⑶VLHIHGTPDCDVKYFVSSSADYSKTYLKNRENFENLVTWFKETKPT VLFIGAGLEEDEILSLLCKDSKNYALMKSENTGNQRVDEHYRGWEGFFSSENHTQIIWY⑶EFEKLPLFVKKLVAD INEKLGTHDFYNQWNNLLNPSINQEEYNKNLDSISNDFKYLSSVLDKVIENDNNQLDQLMLNALLRSETLTVIKKNF VLVFWKFIVKNIEKLSDNEWDVIYKIIYEGSQNYFIDDVFFVYNYAIDNKISSFTNNNKLNELREIISKDGYIVNSN FNKDKTLLGYWLVSAFEQQNRDLYIKEDSEVEVNLNYECVNKLMSILNNPEFLSYNYYSIEHQLKEYDVVKFLYELVKSKKLFIEEEKFLESDSEDLISTILIQKLLVQLDNEINLDLEFIKRLIDKIDFSNIHFGEELNTFIKEHRSIIREKN IEIPKKPYRNWISSLEGGFVSQFSYLTQENLVEYDESRVLEILVNAEKEQRGSSFLEEKTINETENFFITVLKESNE ISKKVSDLLKNHIDDLYPKYKRLYVKIISFPEIEENLRKIVREKYLKRFNKESFDSNDRKFFEYHIKQQNTDIDIFE KLLSINVNELSTPKGDNKQLDILHFINSEMGSYFQCLISLFINHSSYRDVIIQIINSVTDTDYREFAQGILLNEYNP NRINVTYNTFLGFAYYHSTITIEAADVFTDVVRDILNKKIEDNQILNKVYLVALERVDPTIESFSLSKNNYSQMIN IIFTCDYEFRYSKEWLGALFKFDSSANYLVTIFYLLYNENLKKNRFALFIEELSDYLTTYNQKLSLRGMNYKLNHE ELNNFDLLKKMFLKLMETDKIENDIFYLDGIKSILPLLSLDDRRNVLQHIQKQNNCPPPEIEELQRIIVN(SEQ ID NO 842)[2121]>orf01645MFMSNLCQFFQVWNINQGVTQGFNQDKLGIVFDSCFYFLQIINIDKGCCDTITRKEFFQKIEGSTVNSR SSHYMVTSMGKRQNRISHCSHT (SEQ ID NO 843)>orf01646LINVFSHGVDIAIHSATKFIGGHGTTIGGIIVDSGRFDWMASGKFPQFVDEGSSCHNLSYTRDVGAVAF IIAVRVQLLRDTGAALSPFNAFLLLQRLETLSLRVERHVQNAETIVDFLVNHPKVEKVNYPKLADSPYYALAEKYLP KSVGSIFTFHVKGGEEEARKVIDNLEIFSDLANAADAKSLVVHPATTTHGQLSEKDLEAAGVTPN (SEQ ID NO 844)>orf01647MTCDFKFETLQLHAGQWAPATKSRAVPIYQTTFFVFDDT (SEQ ID NO 845)>orf01651MAWLLVGNVGVRQVLEHLNAELKKVMQLSGTQNIENVKPFNSVTSIKPTLPNDPPDLKFIDKKNAPPKC GVFLCYGKKFVLKNKKNEIRIGRIVQDSQIDF(SEQ ID NO :846)>orf01656LKKKffFFADYYDTTIILLALISVILVLLGFAEMIDLDNPPYSIIDLVIWGVFVIDYSWRFFITKRKffRF ILENVFDLLAILPLNAIFTVFRLGRIFRLARLTKLLKLTRLLRIIGLTGKLERKISRFLRTNGLIYILYVNIFIVLV GSSILSWEEKSFSDSLWWALVTVTTVGY⑶IVPVSLFGKTNYRAKEY (SEQ ID NO 847)>orf01666VVDFKQTRQDPHDITIYSWLRQVKSNTGNGSCCVRSNPFQAGNSFIGIWKLATKVSHNLLGCSLHIANS RIITQALPSFQ (SEQ ID NO 848)>orf01671MAERTVVQVHNAFPEDTTLINSQLIPLVQVVVNQGRKGIVGSCNSMHISSKVEVDVFHffQNLCIPTTSS TTLDPHDWTKRRFADSNHGFLANLVQGIRKTNGKRRLSFTCRCWVDGSNQDQFTDWIALNCTNFIKAEFSLVLSVQL QIWRNTKFLYNINNWLQLNTLCDFNICFHSKFL(SEQ ID NO :849)>orf01684MLFIIGHLNFPTAGSFIDSTLHRLGNRVCIHDDMAFTVTSSTSNSLDESTFVAKETFLVSIENSYEAHF RNVNSFTEQVNSDQDIKDTQAQVTDNLRPFQGLDIRVHVLDLDTHFLEVVGQILCHFLGQSCDKGTLIFFNAGIDFT QEVINLSHSRTDFHLWIQESRWTNDLLNHCLGLFIFIVTRCR (SEQ ID NO 850)>orf01685MNVTLKLLPTERTIVQSRRQTETIINQHFFTRTVSIVHALDLPYGHMTLVNHNQEIIWEEVEKRIRRLS FAPSIHVARIIFNPIGIAHLTQHFDIILCPLFQTLGFKQFTFLFKDS(SEQ ID NO 851)[2139]>orf01686MIHFSQHLTCQSLNFTNTVNFVSKKFYSKGMFISGSWENLYHIPTNAKSSALEINIITFKLNIDQVIQE FITRNL (SEQ ID NO 852)>orf01687 VAKLVNLVIDRTILLNIGIARRDIGLWLVIIIVGYEILNCIFREKFLKLPIELTSQSFIVGNNQSWFID FRNDLTHSIGLPCSSRPHQNLSFFSPLNVIHQLLDSLGLIS(SEQ ID NO 853)>orf01705MNITQTDFLAVNLVFAISTTIDMAFHPDFLTCILDKSVMIIQSHNYRSIIERFATFCSSKDDIRHLAPT ETLDTRLPQSPTQTFCNIGLSRSIGSNNCRHTLVKNDLGLISKRLEPLNFDFL (SEQ ID NO 854)>orf01707MSFIVCNHLKFACFNLRNHDLIDKFLDLGHILIQKKGTKKGFKGITKNGVTIATTRFFFPFTQLDKLVK LAITRKTS (SEQ ID NO 855)>orf01719LFTCFSKLDNKTASTTYI SHKFFTAIPVCFEFFKGFffFPRKDTTKKNIFIPMFLVECFNFffVELR (SEQ ID NO 856)>orf01726MTKKIVALA⑶GIGPEIMEAGLEVLEALAKKTGFVYEIDRRPFGGAGIDAAGHPLPDETLKACREADAI LLAAIGSPQYDGAVVRPEQGLLALRKELNLYANIRPVKIFESLKHLSPLKSERIAGVDFVIVRELTGGIYFGDHILE ERKARDINDYSYEEVERIIRKAFEIARNRRKIVTSIDKQNVLATSKLWRKVAEEVAQDFPDVTLEHQLVDSAAMLMI TNPAKFDVIVTENLF⑶ILSDESSVLSGTLGVMPSASHSENGPSLYEPIHGSVPDIAGQGIANPISMILSVSMMLRD SFGGYEDAERIKRAVETSLAAGILTRDIGGQASTKEMTEAIIARL(SEQ ID NO 857)>orf01727VVRNTASHLTCILFLNKGISVYIGNSRSLKHIKIKPCCIKDGFCISVFNSDQNPILGIDSICYRIDSVG HQTNRLVKELIDSIKDCFNGTLPCRIKFDFLTIHIG(SEQ ID NO 858)>orf01729VEAFWIFNHGSSYQSSNICICDFLLLIGQCLELSKEWFDILFCKI(SEQ ID NO 859)>orf01732LANIESHCNFFQSSISSSLPNTIDSPFNTSCTILDSSKAICHCHSEVIMTVRRIDDLTIRLDILNQVFE DGTIFL (SEQ ID NO 860)>orf01741MQEHYTPKGKHLTIDNRRLIERWKNENKSNREIAGLLGKAPQTIHNEVKRGTTLQQVRKGLYKKVYSA DYAQTVYQFNRKRSVKKLILTKEIREKILHYHKQKFSPEMMVNKKQVKVGISTIYYffFHNGHLGLTKADMLYPRKR KGVKKQASPNFKPAGKSIEERPDVINLRLENGHYEIDTVLLTKIKNYCLLVLTDRRSRHQIIRLIPNKTAESVNQ ALTLLLGEHRILSITADNGSEFKRLSEVFPEEHIYYAHAYSSWERGSNENHNRLIRRWLPKGTKKTTPKEVAFIE NWINNYPKKCLDYKSPSEFLLGG (SEQ ID NO 861)>orf01752VHAHTDKLCNGCNRIFNSIISHHTIFRERNKLSHKAIKSTRQEMGPCHVVFIEFFITLHRRLIGNHDNF LTNLVGSGRVRNDGST (SEQ ID NO 862)>orf01753[2162]VNHCHWKLFIQNLGITFSLIVTLIRMTDSHVVGTDKDMIFLVNSLFLIFDIDKLRLS(SEQ ID NO: 863)>orf01755VGNNDILWSKRTISINGFNDFLNTCIAVSTTLCNDDTFLIKRKIFIYKIFCMRNPVSMNTNYNFF NTWL QDKFFNCMNQNRSIT (SEQ ID NO 864)>orf01765LVAPVASSTRFFKNNDSLTSWNNGFIIITINTIISYQRISKGQDLSIIRLVCNGFLVAGHPCIKDDFAC YINICSEGLAFKNCAIF (SEQ ID NO 865)>orf01767VVCYFYITIDWSWVHEDCCFFQTIVTFLSQAMLGMVVFF (SEQ ID NO 866)>orf01768MAFVLHTEKHHDINLINDFINGYKLSIVCKLLTSPFLRSSEKEFRSQAFQNLHIGFGNA(SEQ ID NO 867)>orf01769VVQVTCNSNFKTLKVAKFLINGHQIKQALARVLARTISTIDDGSRNRWTSNQFSIVVDLWMANHTDIHS (SEQ ID NO 868)>orf01770MCPCRILKEEIGNNRMVFIGKLGSIFKLNSSLDQFHYLIDSEVFHGHHMVQCLLIF(SEQ ID NO: 869)>orf01776MSINCKGWNPKSYTHDNIGCLATNTCQTLQFFTCLRDLTIKIV(SEQ ID NO 870)>orf01790MPDCTLTNFLDKVLYNRQGNVGLEQGQANFFGCLLDIRFRDFSFFT(SEQ ID NO 871)>orf01793VQFHLIIFQNLFCSLDIVIDSLTTDTELLGNFSKAVIISVVELDIIHLLICQKRRIKFKERIHTIGFFD FHNFYYTKN (SEQ ID NO 872)>orf01796MKFNHYFFLFLIIEKQVAIISFFMHFHIIKLVNHFQLLIKLNCISHPNLHIRPSFLSLVLLFYQKEQDF AIMVI (SEQ ID NO 873)>orf01799LANNRKTETLGVSYLSTFIDKHELLQSYFESNDKTPVWDGEIHVLKSPSEKKDEILGKVPVQIKTTRQK KDVLKSFSLDTRDLELYKPNGGVVLFVVWLNEDNGLRDIYYKSLPPLSIKNLLKKSKLKNKSTNRKKLSIEIFKLDE KKMYPMLVDFINNSQKQYSFINVEGISVEDIPDDKTLKFYFYGQEKEEIFNYQEEHDLFIYYLDPITGIEIPLENTI KIVETEEETDLIIKIGDYVFQDVKRHRFPDGSVQLHFGESFTMSFDIKKKQFKFNYTRPDLLSKAIKCTQVFQELGK IGYFTLNGNKIELDERSIKDISSLDLEADIKGLLKISNFMKKMGIQKDVDLSCFDKQSQRNLNILYSGLVLKKKVAL NYNESKLLHLNIANIHIITLYSFLSDKNGTMIDIFTETPWCREGETEDEDYLDISIFEVFEPNDWLKIDNCKIDSVI ASYQRLVDNKLKYEGADRTILKIVIAADMAEDKTKRELLLNWAQCLSDWNLKYSKNCEMAIINDLQIKSRVRKLNSK ETETLTNILVNSNDNYELCFGSSVLLKSKPQADLFWNKLDNETKERYKDFPIYTLYMKLS(SEQ ID NO 874)>orf01800[2186]MKVSKKITLFSLSFAGFVLLTLPQAGKAFELKEDWAFKGGIRYENGKVSKINNGYEVNIKVLDLPSTSA IEWTVRLNGEKQNTNFLAEERTVSKTEDKGRFLHFYIPYGYRGDIVVEAKSGNEVKTWSTKVVDDVYSDSAKSGYFI LDGEQILESSWDSVNESYIATLPTVTSGKTVVAWREKGTLNLIKPGRIARQYNSSGSYVELSPIFETASWLKSNQNW YYQKQGQLVQNSWIKDQGSffYFMDDEGVMFNQTWLHQGGSffYAFKSSGAMISADffLYDNGSffYYLKDSGSMVTGffLK NGGSWYYLNKSGSMATGWIKDSGTWYYLKNSGSMATGWVKDSGSWYYLKNSGSMATGWVKDNGKWYYLASSG匪LRN TRTPDGYYVDGSGAffK (SEQ ID NO 875)>orf01801MKKILLSTVALLSLVASLLANNPVSAQESSSQATYSKSSGSWIKSGNRffWYKHSDGSYTTNGWEKINGT WYYFDSEGWMKTGWIKEYGKffYYLDDSGAMKTGffCLVSGSffYYLNSSGVMQTGLQTINGKQYYLAAGGAMQTGffHNI GDDTYFFANSGENQNINRRALVLGETSTRAVPIADVNAMEKVFNNQNFSEVVRFPDRTKSEIIAKMQELFESSSEGD VNYLYFTCHGGRDGRIYIGSDGLAFSGWELASVLKQYKGKFVVMLDCCHAGTIISKDNTGEGNEGASTEYFDLD EFV SGFSNMDGNEKSGEMIDSKFLVLCSSRGAEYSSGGSLSLATKYWSLGSGWNPLQNSQAYLAADQNNNRRITLNELYT YSREQVLKQNSNQHIEVYPDNSQFVLFKK(SEQ ID NO 876)>orf01802MENFGAVLKDIRISKNFRLKDLSCNEISESTISRFENGITKLSINHFYILLNRLGISFSEFEELVHCYY SKKECLFEELEHAVNSSDIFLLQELVDKIELKQKQEKSLCNYHIKLIAEQQINRLANLPYNSSKCNELIKYLLSVDT WMEYELKLFYNSVFFMNTRTISLLYRIVIKKTRYFLKTNTGTHRIIPLYLFNLKLLLKNNLLGSAQFFIDDLENLLT RQGYYFEKNYLLFLKGIYLIKTNQIELGKKECFKAMRIFKEYNDSDTINELNQKFKLDLTI(SEQ ID NO 877)>orf01803MSSIYSSAKKDFLYWNVLIFIMELPNDVKVQFYELRKKVQSFNQLSKRFGMDVSG(SEQ ID NO: 878)>orf01810LSFLILSPAGAQESLSFFFVKITDASKTVKNGGQTETQKLVTKMASDFERVENKDSEVGKIVKEKLALS GDITEAKLTEISSALLAFEKEQNPVDLDAEKEKLVNRLSPRFETLEQAIASKDLEKVREAFKKMNSTWTINESVVRD NSTAHYGRVETAISFLPSSMETEPTDESGT(SEQ ID NO 879)>orf01812MQKNIYFVVLDLHTTDRDKIIQLFKDWTDYSAKLVEGELVKKDGQNALFPPSDTGETVGLNPHRLTLTF GVSASFLKRMNLENKRPRLFRDLPLFPKEQLREKYTGGDIVIHACADDEQIAFHAIRNLIRKGRNAVPLRWSQSGFA AIGDRMETPWNLFGFKDGTANPTKEQDFDRVIWADSKDWMENGSYMAVRRIQMFLETffDRTSLEEQENTFGRYKESG APFGKKNEFDEVDLSLLPDDSHVCLAKEVDKPLLRRSYSYSDGIDEKTGQFDTGLLFISFQKDPDNFVKVQTNLGAT DKMNEYITHIGSGLFTCFGGVEKGGYIGQKLLEG (SEQ ID NO 880)>orf01815MTGKKGFLFLNCHICMVTTTTCFLKERVESELLIFFYISLNRCLITV(SEQ ID NO 881)>orf01818MSLRNKIEQHIKELEGGKFQKL⑶AYLSRKYNFNIVSLGSQEGTDKTTKGIPDSYAVENGKYVYIMYGT HKSVISKLEGDIQSVKKKILEENIAEDKVGRLICCHTSSNITIKQKEDLEKMAEPYHLELIGINEIANDLTKIDFQY LAKEYLSISESTEQVWSINDFIRIHDESKTNAPISNDYI⑶VSEIINTIKSSEKRIFLISAKPGTGKTRLAIEICSL LDRNKYNIICVKSNNQDIYQDVKRNLNLHKENIVFIDDVNTTQNYISTLGLLNTTSNIRFILTVRDYAKKDVINNIK VYGYNNIEPELIKDDNFKELLNQFSRNDFTNQEIEHIKTISKSNPRIAVIAAKLSSSQDLTNFNDEIDILKDYYEEILNKNNIIYAEQKTLFILSYLKKIRLESLEENQEFNKLLKITDITNTDFKSAVEKLHERELCNIYNDKIVKIADQSLD DYIVIKFLINKKISILEILHELYPVNDQRVVQILNQCSNFIRKESDLEGVSDAVKSYYYNESNFESDELKEKFLIQF GVLLPLEAISHVKNKIDNIESQVYTKTNFINQKDKKGSIEDSVLNIVFVTTRTKYCSQILQLLLKYFDKNPNKISEV YSILEANYGLVTEREYIDYTLAENTISELANLDLTKSYNQELIVTILKQFLKIEIERTEAHEEKFTFGRYKVPDSEK LKQYHRSILKLLANLYNIGSCETRFYIEKMLYDYRRKILTYSESHRNTIFGDLRNIRKLFFNDIKNLSMIGEKIVYA LHKAEVKENLPIVFDDYIISDRQKIYNNLTNPNHAWFYDASEIKLQQIANSYSNVWLKIFNFANQFKHSLFMNDNNI ELVLFNMFLLSKNDKKIKFLNYMFKSNYHFVNMNPISFLENIEESSMQSVIVSSPESEKYEWQLAYLTQLENVKNED LQTLKSILEANSLPCYFTILNFERLILKDPSLKELLIQKAGNTNFVISDFIREEEVPKLINLIGVKELKFWYLINLE NCQNHSYNLFQKLGEKDVDFSVEVLKKIDELRIGHSNLGYMVLHSISEFRDKKEIYKKFIRFAINRPYYYYNNMIDD IIKNDSQIILEILEETNNEQSAIRLVNLGVEFLENNNQKLILFNLLRAKGFGKKSFQEIHFTPYSHFYTGSHVPVLE LEKELLERIKKIFETGIDYINLLLYLNKLIDCKRKAIERELEKEF(SEQ ID NO 882) >orf01822MNESLDDITHKQFTSNLTTKADNVSVQLFFSIKGCCHITNQGRTYTWNFIYSVVDTNTSSTDTYLKISL AASYSFPYFFTKDWVESPCMVICTKVNDFISF (SEQ ID NO 883)>orf01824MAISQMKRISLLFSKSSLDDVLKTIQELESVQFRDLKVQDNWSEALEKDEVVFPTIQISHTSNSNHGV IEGNDALIYLMNQQQYLEATVEKLQEYLPKENTFKLVRQPPITTSYKELEKLVKLMLPRVFLKK(SEQ ID NO
884)>orf01826MNRACIIQPSLVEIQIWLLNHVCKCSDFLSHRMRSLLDRKLDLISLLIKLFPKKNWKN(SEQ ID NO:
885)>orf01828LNGGEFLETEFGHSVLAIQSVVWFSFFCLKSNASSLAHGI (SEQ ID NO 886)>orf01829LLAGILELENWGKTTELRPTLLSGPVQNKIEALKRAKI (SEQ ID NO 887)>orf01834MRSQNHNCRPSTRKVGCIGPIFFGHLLNHRKFSYQVLTITLMEEVSLDCLPSGHHVSCQQGSNRYIGDR TCSNSFLIRQFFRQDTTAVAST (SEQ ID NO 888)>orf01861LRQNRCYNCFHDHSCSWKSSRITSLHGCLVRFVGFDIHTHKRFIKSRNGFHDPTNNDGLPISHTTFKTT (SEQ ID NO 889)>orf01862LAAFTITSLKAKTKFHPFKGIDRDNSLSQSCIQFSIPLDIGTKTNWNASDDCLHNPTDGITTTFDLVNI VLDFLFSFLVDNRNFRLGSSLLNFSDCQIFRNIYFLTTKDHDMVGNLHIQLSQEAFGYCTNCHPHGGFTS (SEQ ID NO 890)>orf01863MTWARMSNFPLAFKAVFNVLRRHDVQPFLVVLIDDIHSNRRPCRLPVANARSKDNLVTLNLHTTTTTVA TLTASKVLIDILSCQWKSSWNSLNNSC (SEQ ID NO 891)>orf01865[2220]MHDLAITGSRFDGMANSVAKIEVKTNTIVQLIFNHHLALHLTRMFNQGLCMFQNTLNRTIQSRQESPQF WILNQAILDNFTHPFNQLSFSEGFKNKWINQNPIWLGKGPHHIFSKffCVNACLSTDRRINLSCQTSRNLNKVNTPHI GRGYKASQVPNNATTKSNDSIATSQTLLD(SEQ ID NO 892)>orf01867MVICHNDYLLRLPEFSQPLTSLGHTTFFNLNIIRMMRNIDSDFHRRVSLSLLVFFC(SEQ ID NO: 893)>orf01872LIEGHLVFADKPAQALVLLRKVGSPKKVSFLTLHLYFLILKIDILKITGF(SEQ ID NO 894)>orf01882MSTTTKFNRVVTDSHDTNFLAVFLTKEGHSSHFFSSVNIRFHCLNFKSFPDFFVDLLFNRTQFFSSYR L GSG (SEQ ID NO 895)>orf01887VTWIHSHFNPAVVRIFIVWIVGHVKFFSREIKPFRACQKLISPSDSFVTEVIPDREVPQHFKHGMVTRS LPYVFDVVGTDSLLGIGNTWIFRDNGPVKVFLKRLLPQS(SEQ ID NO 896)>orf01906MNGHFLLLFCLFNIFFHLVNIELSKQVLTVLDWETLVQXXIPFIN (SEQ ID NO 897)>orf01911MRLRDLRRVDFPDPDGPIKAVISLGWKDRETLFKAFFLL (SEQ ID NO 898)>orf01914LKNHSNVFTHFINVDFWTVDINSTIENLPSYFSNINSIIHAIETA (SEQ ID NO 899)>orf01915LHINPLNGFIFTIVNMDILSRKGYFFFRKGKDMLLIPVIC (SEQ ID NO 900)>orf01920LSPFQHCHSSGSIFFNLHFLNRNILQSFDNPFLGLIRENKIEKFCSQLIGLPQCIHMLIRPQGPIIATY IFffT (SEQ ID NO 901)>orf01921MNXXNSRCNHPTffSNFLDILEVDFLGNIVGQKIRSHDLKNPVQVFTVIDMTIHIQVVKTNMVILADRLF QGFILRSTDKFFIKIRLVRSHNLRFNNMDFSTVAVHENKGRHHVDELLPRFIINSKATVAKKSIVAQGFRFDGNFFR KTRQTNHLNIIFCDNPDQIIVFQNGLITNSQFNRLHP(SEQ ID NO 902)>orf01930MWYFYNTDGSMATGWVQVNGSffYYLNSNGSMKVNQWFQVGGKffYYVNTSGELAVNTSIDGYRVNDNGEff VR (SEQ ID NO 903)>orf01931LTFIKSWAIEIFCFDWNFLDKNLGLGSFFNNSCLRVFFLT (SEQ ID NO 904)>orf01932LLLSCRKVIVCFIFSSKWNKNFFNLAFSWNFDNCIRGFFSINSNLFGNITSLWINIVGPCRSYIAILSI NCNRIFTTVFCFIFFITNSRT (SEQ ID NO 905)>orf01949MRFIVGRFTSFSLGIEFSPTSKLDDLLFKIAFLMILATWIKARKTKGAT(SEQ ID NO 906)[2249]>orf01961LVNCEPLEAYRQLEEAELVGCWAHVRRKFFEATPKQADKSSLGAKGLAYRDQLFALERDWEALPADERL QKRPAPNGRLLCLVPPSVSFSRFKTRKGN(SEQ ID NO 907)>orf01963LKRNKIffKKTLTYPVEREEITYKRKKAKGKRQAILAQFDSEEVHHRLENCICPDCQGELKEIGASLQRQ ELVFILAQLKRVNHIQHAYKCQTCSKNNPSDKIVKAPIPKAPLAHSLGSASIIAHTIHQKFILKVPNYR (SEQ ID NO 908)>orf01964LKIIQQQSATIDSLTNELALLREQVAYLTQKLYGKSSEKSVCPSGQLSLFEEEQNMEEDSDLPS (SEQ ID NO 909)>orf01972LICQTIKYWHKFHLHIGRCKLLIGLIPILNFFIRADIDCLLVLLSLIDRQNGKQFNLCQWIIASNGLND SFEIIESLIHRNILSDIICPNQKKNFIYCSTI(SEQ ID NO 910)>orf01978MSFSCSDSCFSILLLDGDIHENTTFSPLSILFISHRFNSLIGNEVPHLIDNELLISIFFHRFRWFNNVR MPSKDNIRSPIDHLVIKSFLFFSWFQSILNTHLKHDNGDICFLLCPFNFSLHLIFV (SEQ ID NO 911)>orf01981VVEQIPVGHNSGSFFLFLLLRLLLSPLLRNSISFLTSQGIPWKLSNNKTKPIDKSTASKSIATNPLLLH LR (SEQID NO 912)>orf01988MLKLIIYQFQYSKRQWLGTIPLLFVSSLIVGTSLFGIASSIKTANINASQLFQMLIIFGGTTLFFLIS NNIRLLIDIFKKDYQLWTILGASRTQLSLLVSGQFYLMAVIVSSIGTILSFIMADSYYKFLQNLLGRDELPDLVIT ANIQSILLSIFIVPTIVGIGAYFYSSRILKISSILKPKKKKRKVTVTGFVNISVRLFLWLLCIGSIVSAGFIRNKEI IEKQSSIILFLLIIHILIIQSLSPSIQMFLIKFLMRIFPTENYVINTGFWNLLSNPSYLKSIQTSMSMGVTLISGFI LYTQ匪YSFMNTANGVNEARASFIAYMSAPIILIITSSISLTILSSNKDIEDIKQLKTLGVSRLQLFKIRIGEAII HSVLILLVSVIFNLIILILVSIIGQFLGRSLVDISGFWQPSLIVISLLVIFYSITKGFYLFQDR (SEQ ID NO: 913)>orf01989MVNNVAVKVSNLSKEFLLGQDKTVSILKDISLSVNYGEFVSILGVSGSGKSTLLSCLSSLSEPTSGEVV INGVNPYTLKEGKLAKFRRQDIAIIFQNYNLVPALPVLENVTLPLRLSGKSVDSNKVKKMLDSLNFKAELSSLVATL SGGEQQKVAITRAIIADSKIIFADEPTGALDSVSRKLIFETLRNLASQGKCVLMVTHDIELASKTDRALILKDGKIS RQIIKPSADELYQALESSKD (SEQ ID NO 914)>orf01994LALVRKFIDYFFGVLVPFPDLYVFKSCFKFAGSFTDFDTFDWWLDWCRSCSENRFFV(SEQ ID NO 915)>orf02006MPTILLLKKFYERLITNFFRLKFLFCKEILATNIFNHPLFEPDIRVITIKII(SEQ ID NO 916)>orf02009MXXGAFGQGELLLQQSRNSSITEIVSDSWAGAGRRILPLPKSVTPLVSS(SEQ ID NO 917)[2271]>orf02013MLLLISLTQLIIFLFFERFNLLLKTFLLVDLKSNKSA (SEQ ID NO 918)>orf02022MAGKKGFLFLNCHICMVTTTTCFLKERVESELLIFFYISPNRCLITVYSVLNL(SEQ ID NO 919)>orf02029VIPRYVTKHQGWDHNPHTITNSDDDPATLVTFRTFKFNVGNCTIPKNDQNGSSQKFSGILQCPCEIHLL DSP (SEQ ID NO 920)>orf02034LLVRKFNIQTFFIQVFILNDFGYTVNGLIVYRLLLTSSILSFNDYSIGSFRTVIVI(SEQ ID NO 921)>orf02040MRLSIQLIHDLNTHTTHSTAKMLYNVKAIKNDFSIRE (SEQ ID NO 922)>orf02048MTAQLPSDALQMALWRRKRPRNVIVHTDRGGQYCSADYQAQLKRHNLRGSMSAKGCCYDNACVESFFHS LKVECIHGEHFISREIMRATVFNYIECDYNRWRRHSWCGGLSPEQFENKNLA (SEQ ID NO 923)>orf02093MEIVLVSFSISFQHFIIAYCLDFSSAGFRNSQNFSNFC (SEQ ID NO 924)>orf02105LTEKIQEHELIKTNQAEKSVQDVLDNCIERVQNNSLKSDRVTSFETPFALLFIFATIAVMLTYGGYRV SAGYISVGTLVSFLIYLFQLLNPISNIANFVTVYSRSKGSSVALENLLAVPKEKFEGGKSVSGRGLNFNHVYFGYD ENRPVLKDITCSIFKGQKIAFVGPSGSGKSTIVRLLEQFYKPLS⑶ILMEQSSIYDFNLKEWRSKIAWVSQNNAVL SGSIRDNLCLGLNRLVTDDELMKVLDLVSLGDEIRSMKEGLDTEVGERGRFLSGGQSQRLQIARTYLKDAEILIFDE STANLDADSEYAIISILYSALKEKTVVIIAHRLSTVKDVDCIFFLEERKITGSGTHKELLENHERYARFVQEQMIE (SEQ ID NO 925)>orf02106MKLKLLRVDTKVIMGSFLLVLSSLLALLLPLILKGLIDGSSIENIGSKVFQSFLIFIGQALFSSIGYYL FSQSGEKKIAKIRKKVIEGLIYAEKSFFDKSQSGELTSAIVNDTSVIREFLITTFPNIILSLVMVLGSIVVLFSLDff NLSLLLFITLPCMMF11LPLSNISEKYSRRLQEEI (SEQ ID NO 926)>orf02115MXXALIPRVSIGSVGLLLLTENYVKGDLKAASRLVQDSLTLLFMFLLPATVGVVMVGEPLYTVFYGKPD SLALGLFVFAVLQSIILGLYMVLSPMLQAMFRNRKAVLYFIYGSIAKLVLQLPTIALFHSYGPLISTTIALIIPNVL MYRDICKVTGVKRKVILKRTILISLLTLVKVSVNRNHPVAVRIFLPTKWTFVELPLCSSCRCHGGWTLYGYESAYLF IR(SEQ ID NO 927)>orf02125MRERVRLSGSLFTSLKTREHIKSTMELFHKYVFFLIQEIKIKMINFLKIGDLPTL(SEQ ID NO: 928) >orf02134MANHLYIVPIQVNHKSSIVNRMLTSITRNPIVSPTCLYASLITSLNFFLIFC(SEQ ID NO 929)>orf02137[2296]VIVFLSRNKDGNAFCHLDLISIANPVWGWDDDFITWIDHSHKEGIERIFGSRSDCHLI(SEQ ID NO 930)>orf02140LSNQFYFSLQTKPILKVKQFLLFQSQMTRVSEILQFSNKL (SEQ ID NO 931) >orf02141MSKKVLFIVGSVRQGSFNHQMALEAEKTLAGKAEVSYLDYSDLPLFSQDLEVPTHPAVAAAREAVLVED AIffIFSHSLQLLYPRYSEKLA (SEQ ID NO 932)>orf02144MEDKEMGFYLMVASMLLGLLALKIGFSQFKEKKDKFLSILTSLAGTALVLVAVffLGffPK(SEQ ID NO 933)>orf02166MLDSDIGCSRKNLLGLFWIRRRRNIHIVDRAMEKGISNRAPNKISLKACFFNFF(SEQ ID NO 934)>orf02193LLHPFTRNITCDRHILTLLGNLVNFIHIDNATLCTFDVKVSNLQEFEEYIFHILTHITSLRQSCRIRNS KRYIQALSQGLGKESFP (SEQ ID NO 935)>orf02194VEIDAFVVVINRHCQGTLGTILTNYIVVQDMEEFNWFWHLRQVCQDFLNQFFSNDFLS(SEQ ID NO: 936)>orf02198MEXXXTELAGRGFLVffHPKMDEYMEALDGHLDEISERLITLGGSPFSTLTEFLQNSEIEEEAGEYRNVE ESLERVLAIYRYLITLFQKALDVTDEEGDDVTNDIFVGAKAELEKTVWMLAAELGQAPGL (SEQ ID NO 937)>orf02199LITRLLHRVHVLVDDFNPSICITWSSLALIYIFPVLNIIIDRVRQVHIVFLYKSHGLFSVILSIGLIFS IGIEIDTIRNSQNG (SEQ ID NO 938)>orf02200MXXTGSLSANFAGSTTASSSSEQNQSSNKTQTSAEVQTNAAAHWD⑶YYVKDDGSKAQSEWIFDNYYK AffFYINSDGRYSQNEWHGNYYLKSGGYMAQNEfflYDSNYKSffFYLKSDGAYAHQEffQLIGNKffYYFKKWGYMAKSQ WQGSYFLNGQGAMMQNEffLYDPAYSAYFYLKSDGTYANQEffQKVGGKffYYLKKffGYMARNEffQGNYYLTGSGAMA TDEV MDGARYIFAASGELKEKKDLNVGffVHRDGKRYFFNNREEQVGTEHAKKIIDISEHNGRINDffKKGIDEKR VDGVICRLGYSGKEDKEffRIH (SEQ ID NO 939)>orf02202MHKNFVVVVTNFFTAVQFIQFNKEGTTCHNTTKFFNHLDSCLNSSTCRQKVIYNKNTLTWLNGIRVHS QGIDTVLFFIVSRNNFAWQFTWLTNRRKTNSQLKGNWTTHDKSTSFRSHDHVDFLVSSILNDFTNSVAISISISHQ RTNITEGNAFLffIIFNCCNVIF(SEQ ID NO :940)>orf02209MNRCNSRQAIffKIISTLNRENTHIMLNRQVCFCFVNHISPLNVVIWENLSLEELLYAICICFITHKIAK QTSLTIDNAGIAMNNIR (SEQ ID NO 941)>orf02214LDSRFFCTDFFKGRQAKGCSFSCTSLSLTDNILAFKGQRNSLFLDRTSFYKTSFFNFC(SEQ ID NO:942)[2321]>orf02225MGRKPRTRPEERTELERLQAENEYLRAENAILKKLRELRLKEEKEKEERQKLFKN(SEQ ID NO:
943)>orf02246MLSKEEYIEEIGLIEKQNYVEVELYPLVADIINPTLKNSLSKRYVFGRRKSNMGQIYYGLSNFPDIVIL DKNYQNKARKSIEIEEWKKLRGCVEIKSLKHDLITEEKIKSTISNSFEHITGEMGQLIGDLLWYKKVIYTNGIEWRF LSLDDKEEIDNTIVQVVNKRIETEEAGNSFDffffKNIKDLSFNYTDIYLSKDCIQEWDEFVKKVKEIEW (SEQ ID NO 944)>orf02248LEVCIHHHHQISCRILQACIKGCFFAKISRERNIMDCRILLPIGL(SEQ ID NO 945)>orf02255VDRTDEVSSKHCFEVVDRTDEVSNHTHGKATLTWFELDFRRV (SEQ ID NO 946)>orf02263MTPIKDKVRRVKTPMMVNPDTDLTISSVQQDYFSLALIGFSLLTCDFLSFSKOTQKTGLSAFIKICHLI KIARLDNKITKQQEYWLYDLLMMSQGEKIQKIKQLKQVTSDILLNTPDFSSYFEKYNFKEEAENIKSYLLAKSMDKS GRLFPSNEFGEFVSPVSFQHGFGGVLFFMNKYYVEEDENTVKEWLTKLENYEAANFLHGYSLLFGKAGFLFGILDRY EKTKERYLIDISKRLVDHLMRVYDNISNLDFALGKSGILLSLMKYCTIFDDKKLANFIKNNINDAYSLLESEDNGDI YSNNFAHGRSGAAYVLKAYTDIFGDSRYQNHLQKFSDGISELLEEKLSSFSKLDNLGLSWCDGVSGLILYLCLIDKE RYSEIIYKSQLEMVQQYEAMGTSFCHGLSSLLQTTIYNKNQKVEQFIKKILLTRSYRNNDRLLQFQGEDGINSYFDF GVGNLGIYffTLLGYTFPFELSKGD(SEQ ID NO 947)>orf02264MHIFLKNRAFRQLTVNEWISSF⑶TIFYLAFINYVSSYAFAPLAIFLISLSETIPQVLQLFTGVIADFQ KNRISKYISILFIKVLLYSGVTLLLTSTDFSLFSVFFICSMNLISDTIGFLAGYMLTPIYIRLINDDMTEAMGFRQS TSSIVRLIGNLSGGVFLGLFSISTLAFVNVLTFLFAFLGSLLIRNRLKKEEEKIEVPPYVGMSSFFQHLKESMKLLM TMEDVMVLLffILSISQAVLMMVEPVSAILLIHHPFMGLSTGQSLAILIMISLLHVILGGLLSGFLSKKISIRLNIYff SLLMESLIVIDFLRGSFLLILLGSA⑶AFSAGVLSPRLQAMIFGIIPEELMGSVQSSINVINLLIPAVLSLALVFLA TSAGLEVVAFALIILLLIAAYLVHQMKNLPNQEEV(SEQ ID NO 948)>orf02266MTVPDRLPARMRMDGRSIFQQIKNYFDTENKEYFKHPNTYDGISMHLEPNILTSMEHFDLTGFHCECKD FQNQGVCKHWVAMDLYFRSLPQAIQERIGKASHKPSFASQLIPTLPSEELQDELVEEKATAPSLALHGQVEIRNHSL AWTLKLQVEQAPRAYVIKDIAHFIFLIFQKEDYFVSQKIGTIRLSLNQFNQASQNLLLYIKKYFIDRNEHSYFNFSY GINPRDYGRYLETPVSYLNDLVPLFQALDVFQYVTSKAEYPLIFLDDSPFIPEEEIFKVVKSNNHYEIINTAYFGFI IQEKLWIRHNHFHIIKEEHRYFLDKLATWIYHYQENSPLIFSKENKAELMQVCNIISNYVPISIPDELQIHDFIPTF AFSKTRNEIALNMVWSFGEKQVHSKQDLLTLPYTYQASKARKIYHQLLSAGFKEEFHSLSKIKIVDFFLKELPRFRT LGQVQLDESLEKLLVEDPAVIDIFDDESFLSVQFDFSMISEDEVEKAIQALWNQESHYQTKQGKVLVFDDESLKVAQ SLQDLRAKFSDGKIKMHKSRAFSLSETFKDNEHVNFSRDFKKMAYDLTHPEEFDIKPYEVKAKLRSYQKEGVKffLSM LDHYHFGGILADDMGLGKTLQTITLLEANLKPDQKALILAPASLLYNWKEEFRKFVPHKQVEVAYGSKTERIKQIEK SATITITSYPSFRSDLEHYQKQSYDYLILDEAQMIKNSQTKTAQALREFDVKTCYALSGTPIENRLEEIWSIFQIVLPGLLPSKKEFSKLSPQLVAKLIQPFVLRRKKDEVLTELPELSEHLYSNELSSSQKTLYLAQLRRMQEMVSGASAYEI KRHKIEILAGLTRLRQICNTPALFLEDYK⑶SGKMDSLFELLDTIREKGSRPLIFSQFTSMLDLIEQELEKKEMSHF KITGQTPSDKRQEMVNLFNQGEKDCFLISLKAGGTGLNLTGADTVILCDLWWNPAVEMQAIGRSHRLGQTKQVDVYR LITLGTIEEKIQELQESKKELFNTVLEGQESRSNLSVDDIKEILGVE (SEQ ID NO 949)>orf02283 MMSMVDPIDQTFIVNLKIGKSQVFSQLQFSCHIVVYPSEVHIYQAFVIKLQNHILGPQVLP (SEQ ID NO 950)>orf02284LPNRTRIDNQLPTSPVTKQLLVNMSINSNITGRMSHQAVKLLLFASMNQLSPPVLIRQMMANSHRQIPK LTMNLKRLIVEHFNFF (SEQ ID NO 951)>orf02285LIQQVQNPSTPCPWHENISQKPVFIHSYLPSICQNSLQGGGISMNI(SEQ ID NO 952)>orf02308MIDKVVRNLLLTFLFCKMTKIINFLTTILVKKKKMCYNVSKLREKKKGAMMWVLGFILFIIFFYSNNSK KIKKLRE (SEQ ID NO 953)>orf02309VDRTDEVSSKHGFEVVDETDEVSNHTYGKVKLTWFEEIFEEY (SEQ ID NO 954)>orf02314MIAEFIDGLQKFHFLQNALITAIVVGIVAGAVGCFIILRGMSLMGDAISHAVLPGVALSFILGLDFFIG AIVFGLLAAIIITYIKGNSIIKSDTAIGITFSSFLALGIILIGVAKSSTDLFHILFGNILAVQDTDMFITMGVGAAI LLLIWIFFKQLLITSFDELLAKAMGMPVNFYHYLLMVLLTLVSVTAMQSVGTILIVAMLITPAATAYLYANSLKSMI FLSSTFGATASVLGLFIGYSFNVAAGSSIVLTAASFFLISFFIAPKQRYLKLKNKHLLK(SEQ ID NO 955)>orf02336MYEEPEVAPVHPTGPTPATETVDSAPGFEAPQESVTIL (SEQ ID NO 956)>orf02363MGNNGQFTFGYRHDFFQNQLAIFNALVDTFTRRTIDIKTLNTFINEVLNQGTRTLWTYFSLLIITCVEG WNDTFVFFQI (SEQ ID NO 957)>orf02368LHEVVIPSIDEGKDCKGCKPWFHNREGYTPEGTNLTTTVDFS (SEQ ID NO 958)>orf02369LFHEEDTEWPSNQRQDNCPESIVDSHEVDDTYQWYKDNLFWKRHSSDKDSK(SEQ ID NO 959)>orf02393MSYFRNRDIDIERISMNRSVQERKCRYSIRKLSVGAVSMIVGAVVFGTSPVLAQEGASEQPLANETQLS GESSTLTDTEKSQPSSETELSGNKQEQERKDKQEEKIPRDYYARDLENVETVIEKEDVETNASNGQRVDLSSELDKL KKLENATVHMEFKPDAKAPAFYNLFSVSSATKKDEYFTMAVYNNTATLEGRGSDGQQFYGNYNDAPLKVKPGQffNSV TFTVEKPTAELPKGRVRLYVNGVLSRTSLKSGNFIKDMPDVTHVQIGATKRANNTVWGSNLQIRNLTVYNRALTPEE VQKRSQLFKRSDLEKKLPEGAVLTEKTDIFESGRNGKPNKDGIKSYRIPALLKTDKGTLIAGADERRLHSSDWGDIG MVIRRSEDNGKTWGDKVVISNLRDNPEAKDPAAPSPLNIDMVLVQDPTTKRIFSIYDMFPEGRAVFGMPKTPEKAYE KIGDKTYQILYKQGESGHYTVRENGEVYNAQNQKTDYRVVVNPTEPGYRDKGNLYKGQELIGNIYFAHSTKNPFRVANTSYLWMSYSDDDGKTWSAPRDITPGLRKDWMKFLGTGPGTGIVLRNGPHKGRILIPVYTTNNVSHLNGSQSSRVIY SDDHGKTWHAGEAVNDNRQVDGQKIHSSTMNNERAQNTESTWQLNNGDVKLFMRGLTCDLQVATSKDGGVTWEKDI KRYPQVKDVYVQMSAIHTMHEGKEYIILSNAGGPKRENGMVHLARVEENGELTWLKHNPIQKGEFAYNSLQELGNGE YGILYEHTEKGQNAYTLSFRKFNWDFLSKDLISPTEAKVKRTREMGKGEMGKGVIGLEFDSEVLVNKAPTLQLANGK TATFLTQYDSKTLLFAVDKEDIGQEIIGIAKGSIESMHNLPVNLAGARVPGGVNGSKAAVHEVPEFTGGVNGTEPAV HEIAEYKGSDSLVTLTTKEDYTYKAPLAQQALPETGNKESDLLASLGLTAFFLGLFTLGKKREQ (SEQ ID NO 960)>orf02395VADRTDEVSSKHRFEVADRTDEVSSKHRFEVADRTDEVSSKHRFEVADRTDEVSSKHRFEVADRTDEVS NIYTARRS (SEQ ID NO 961) >orf02399MKIKEQTRKLTAGCSKHCFEVVDETDEVSSKHCFEVADRTDEVSSKHCFEVADRTDEVSNIYTVRRR (SEQ ID NO 962)>orf02407 MSCNCAFYRSQFFDVNSVSNYHSHQKELRFPNSILFTYFVKVA (SEQ ID NO 963)>orf02428VGLIKLTSYVFVCISNSFLTRHDKNDNICFFHGNFCLVLDLFHERSIDIINSSCINHAKRTIEPLTRCI NTVTCHSFDIFYNGDSLTSDPIK (SEQ ID NO 964)>orf02430LSSKSCIDRTNQETFHTLGLEGVGMKSGSLFCSVQISDKEKENSRLANGFLRYQFIQGIFLLLTSYHNH RVGLEILPR (SEQ ID NO 965)>orf02448MKSKEQTRKLAVGCSKYSFEVADKTDEVSSKHCFEVVDRTDEVSNYIYGKAKLTWFEEIFEEY (SEQ ID NO 966)>orf02450LSNSFFLIKFSSSKTSGKKRIVSDNIFIRNKFICHFKKE (SEQ ID NO 967)>orf02459 MDYSKVAAEVIEAVGKDNLVAAAHCATRLRLVLKDEAKVNQAALDNNADVKGTFSTNGQYQIIIGPGDV NFVYAEIIKKTGLKEVSTDDLKEIANKDKKFNPLMDLIKLLSDIFVPIIPALVAGGLLMALRNFLTSPDLFGPQSIE DMYPAIKGFSAMIQLMSAAPFMFLPVLVGISAAKRFGANQFLGAAIGMIMTTPDLGGKEAFWDILGFHVTQTNYAYQ VIPVLVAVWLLANLEKFFHKKLPSAVDFTFTPLLSVMITGFLTFTVIGPVMLVVSDAITNAIVWLYNTTGAFGMGLF GGTYSLIVMTGLHQSFPAIETQLLSAYNNNGTGF⑶YIFWASMANVAQGAATLAVYFLTKNAKTKGLSSSAAVSAF LGITEPALFGVNLKYKFPFFCALAGSAIGAFVAGLTHVIAVSLGAAGFIGFLSIKAGSIPMYIIAEIMSFVAAFAFT YFYGKTKAASVFADEAATATAETVTEPTVEAPVVEETDTLQNETLVTPIVGDVVALADVNDPVFSSGAMGQGIAVKP SQGWYAPADAEVSIAFPTGHAFGLKTRNGAEVLIHVGIDTVSMNGEGFEAKVAQ⑶KVKAGDVLGTFDSNKIAAAG LDDTTMVIVTNTADYASVAPVATGSVAKGDAVIEVKI(SEQ ID NO 968)>orf02466MTESYTWVEADRATLSRYRHGQGHLTDQFFSFKVQRPAAKTLIASISTGKGMGPSFDGTPVITSGNQ NRINTIKNSFIMSSSSVRISLRKLTSQRNFLRNLSSLILLAAQVAKGDATACSHQRISRVVGQDSHETLSLTEFF (SEQ ID NO 969)[2374]>orf02467MNlNNEKVffFAFYLLDMQITRPTPTFNDRRIGLIGKLQELRFLAGNLLLR(SEQ ID NO 970)>orf02468 LIKGYLPNHLALMDLCSKTTCTLDDFAGIAGRRNHRGFFCHIGNGVFLTVDKYLRNQRIRQRKSSHHIL TQLVCHSHTHLFILLQTSLSLRTKERLSF (SEQ ID NO 971)>orf02474LIKLTGRNFSDILIKCLVKCFTNLLSNQLMLLPSTLKL (SEQ ID NO 972)>orf02479MIESENHCSASHSNRDYQSQHDNQGRTCQCFIIVPCHKKGSCSVGEITWNQRCQNGQDKDHSRCLIKNT
(SEQ IDNO 973)>orf02486miarqlmvffstnqadtri msidsliinnskdfqssshasvsfiltklvnllifnf(seq ID NO:
974)>orf02487MGEPFTHFIDCIDLGINPSYTQVCDRHFTSDIPCTMTSHPIS (SEQ ID NO 975)>orf02494LSSDSHFIGIKAFVILILGKSNSIVLRIVGLYQDLTCFFSPTCSTCHLSQELEGSLRRTEIRQIQGRIR I (SEQID NO 976)>orf02495MAVHSLGIHMQGQRNIAVGTSIHRPTLPTHDKARITTAIEHENHLLFFNQTVLDSL(SEQ ID NO:
977)>orf02496MVTGIAVLLISHFMLFINNHDTQIFQRSKDSRSGTNNNLGIATLHLAPFIILFTIG(SEQ ID NO:
978)>orf02497VKNGYLVPKTCYKTLGHLRSQGNLRYQQNSCLALIQGTLDNLQVNLGLPTSCNPLK(SEQ ID NO:
979)>orf02498MVNLIPRLGLDLLLIDCLIFQTKQAFSSQTHHFSLLGKV (SEQ ID NO 980)>orf02499LGLQTKNNPLNQAIPLTKRHMNPHPNFQHSLKFLRNPVTIGLVRLHQGHIYDNLS(SEQ ID NO:
981)>orf02502LGNHFCTICSTTYQAILQFIQIffffCQEDKDSIWNLFLDLKSTLNFNFKENIDSLVQGFIDIGQRSSIVV ADIFCVFQHLSLTNQLFKFFTSTEEIVNTVHFSRTLCACRHRYRILKLVFRTLKNLSSNRSFSNP (SEQ ID NO
982)>orf02527VGCSYICHELVTNHDHFLFVIVEFLHSTVNTKCEGLQGPVNVINPKFLNCSLNAFFGVI(SEQ ID NO 983)[2402]>orf02528LLHLWRSIRVVPSNGGIIQIDQNSLDSLRLQAffDCQIIDCFHSKIffYIIFNRHSGSFC(SEQ ID NO: 984)>orf02530MIGTFAAALVAVLASFIVPIEITLNSANTEIAPPDGIGQVLSNLLLKLVDSPVNALLTANYIGILSWA VIFGIAMREASKNSKELLKTIADVTSKIVEWIINLTPFGILGLVFKTISDKGVGSLANYGILLVLLVTTMLFVAPM VNPLIAFFFMRRNPYPLVWNCLRVSGVTAFFTRSSAANIPVNMKLCHDLGLNPDTYSVSIPLGSTINMAGVAITI NLLTLVTVNTLGIPVDFATAFVLSVVAAISACGASGIAGGSLLLIPVACSLFGISNDIAIQIVGVGFVIGVIQDS CETALNSSTDVLFTAVAEYAATRKK (SEQ ID NO 985)>orf02537 MWNKNRQLRKVKKILNQINRRKEEMALLTDEELAAKTQEFKRRLTAGETLDDILVEAFAVVREADKRIL GMFPYDVQVMGGIVIHQGNVAEMNTGEGKTLTATLPIYLNALSGQGVILVTTNSYLAKRDAEEMGKVYEFLGLTIRL PFADDEEEKITPKEKKEIYSADIVYTTNSGLGFDYLIDNLASSEEQKYMPEFNFVLVDEIDSVLLDSAQTPLVISGS PRVQSNFYGIIDTLMTTLVDGEDYIFKEEKKEVWLTNKGAKIAEKFLGIDNLYAEENNVLARHLVFALRAHTLFKRD KDYIIRKGEKDQELVLLDQGTGRLMEMTKLQGGLHQAIEAKEHVKLSPETRAMASITYQSLFKMFNKISGMTGTGKV AEKEFIETY匪SWRIPTNRPRQRIDYPDNLYITLPEKVYASLEYIKQYHAKGNPLLVFVGSVEMSQLYSSLLFREG IAHNVLNANNAAREAQIISESGQMGAVTVATSMAGRGTDIKLGKGVAELGGLIVIGTERMESQRIDLQIRGRSGRQG DPGMSKFFVSLEDDVIKKFGPSWVHKKYKDYQVQDMTQPEVLKGRKYRKLVEKAQHASDSAGRSARRQTLEYAESMN IQRDIVYKERNRLIDGSRDLEDVVVDIIERYTEEVAADHYASRELLFHFIVTNISFHVKEVPDYIDVTDKTAVRSFM KQVIDKELSEKKELLNQHDLYEQFLRLSLLKAIDDNWVEQVDYLQQLSMAIGGQSASQKNPIVEYYQEAYAGFEAMK EQIHADMVRNLLMGLVEVTPKGEIVTHFP (SEQ ID NO 986)>orf02538VSNKLHILQIGNRNWSHYYEIPENIEWHFFWPGSTTAIKKVMKMEGIRTFSGVVIENPDYLPDLLPLIN ILTPYTIFYSDICASYSPLVEEFLKKTCAQVTDFSNPRELLRILSKALFKGQY⑶KLTPIDMWNPYFAGSIRYNGY ENLELVGSYGEDFRPLISWKYNIRASEWNPIELWLEYEKDLSCDIRIWRNIQDGSTADFIKERIFTTDDMEAAILL DDDFSSFISVSLEAKGNGRLKIGALHQRLTRYQFGKFVLGGNIIRSKNREEINYFFYPGDFKPPLNVYFSGYRRAEG FEGFGMMKSLGSPFLLFQDPRIDGGAFYL⑶DDFENAVRRVIQHHLDLLGFSNKELILSGISMGTYGALYYSSDFEP KAVIVSKPLTNLGLIAERGRLEAPGLFPTAFDILRHHSQGKADIDSINILNARFWERFRGADFNQTIFGLSYMKEED YDPIAYDSLVDSLYSTGARIMVKGTSGRHNDDNDSTILffFVNFYKMVLEQEFGRKY (SEQ ID NO 987)>orf02539 MYYFIPFLESMNQSWQVDIVPWYQTTHRLEFDDVLHQIRIFKREGIKSKIVLLPYHPHMRYLLHRQDLL EVEAFSVFDAIQDIENEEIYPLQLKDLAWDEDCDFIYTPFLIAVKQKGELHAHIEFGTEGFISYITYFKDNQVDFIC YFDDRGFLSSLVKYQDNQAVSRYYYNSNAEWQIKEYLQGIHTKVEVNPRFSHRFRKSTYQSMDEVVffEFFEKFLTAE YKEGESFVLAAQTKYQNQLLKHLPEHADKILTFFIERNQEDDLNLHHQAVKQAKILISDRQDFLERLKQHYPQFTYK MHHLPSFDTRLKLGVSQRVKESKLYVQLDLNTPLNSEALYEVLNFVSQNPLTEIVFATFNAEGYQIEALQKHLFTLI SERLNFRDLLKESIISGAENKLEENKEENYRFQIVNLNDEIGLIRELEYTRLIVDLNPIANIYTQIAGISAGIPQIN LSESEYVTHLQNGYILSDLSEFSKAGHYFLDTLEHWNQALIHSIDKIRQNTGNQFVQKWERWLEEAKSEQ (SEQ ID NO 988) [2412] >orf02540[2413]LKKKLKSVVVKRVMWTICFIFVYILGSRLTLPFVNVNDTSFLGGNAAFLAFSTAMTGGNLRSLSLFSVG LSPWMSAMILffQMFSMSKKLGLGNLPLEIQERRKMILTFIISFIQTLAITLNLPIQEGVNHDLVLILNILLLISGTF FLVWLSDLNSLLGVGGSVVILMSSMIVSVPENIVRSIIDLHVNLLFIISLLLISIAFLYIAVRVQKARYRILVNKIM IHNRFKRYSYFDIMLNPAGGMPFMYAISLVSIPQYLLMLLHIFVPKTRWVDNWIAEFTIGRPVWVYTYIIVLFLLGI AFAFV匪NGEQIADKMKKSGEYIYDIYPGEDTALYINRLVLRFAVIGSIYILLMAGIPMLIILYEPRYMOLSMLPGL FLMFNGMIFNVKEEINALTLNESYRPLVERK(SEQ IDNO 989)>orf02541MKINITNIYGMSGQSTALIAQNETVKIAKKLDFHELSFYFYNIYSDSEGELNSRLDGVLAKLGY⑶IW YQSPTWNGREYDQAFIRKCKILNTRIITFIHDVPPLMFPSNYYLMSEYIEMYNQSDLVVVPSEKMKERLIQEGLTVQ KIIIQGMWDHVHNYPLKQPSFQKKLSFAGSVERFGHLSNWSYSTPLDI FSESNYENSNPRVSFKGWKTDPELLFAL SEGGFGLVWGTNENPADEEDYYRLNISHKVSTYLAAGIPVVVPSYLSNASFIKEKGLGYVVDSLEEANRLVEETTVE VYQQMVENVSKVSYALKEGYFTKKLLTDAIMQLLDI (SEQ ID NO 990)>orf02543MKAIVLAGDKNYLTPILTTIKSILYYNQNVKIYILHQDIPSDWLQELKIQVEKLGSVVEGIYI⑶AID SEffKTQAHISPIAYARYLISRLITEDRVVYLDSDIIVN⑶LSPLFELSLGDYSLAAVRDVDGNGFNSGMLVIDCQK WREKDVTSMLFDKTVEYMSYLDHTDTDGFN⑶QTIFNLVFQNHWLELDKRFNFQVGHDIIAFYSHWDSHFELDEE PLIIHYTTYRKPffTTLMGYCYRDLffffSFHDVTFDQISDHYQGRFAVKRVYDFHDINLFTFTDSQDLLYIDELAQS LLDIAFHIGAYTDM⑶ILLALDKYPNVYLYPSMVGAVIDEMIEKSDAYLDIHKGSSMDFIVNRYTSAGRPVLTFD VTNKNQLEEIVVPSQSPLEMIKVIKKLKSDKMETKAIVFGANYQYADKVLTTIKSICCHNRGLRFYLINSDFPTE WFYNLNRKLTKLDCEIVNARVNSSHISQYKTNIHYAVFLRYFISDFVEEAKVLYLDCDLVVTRDLSPLFDLELGD YPLAAVKDLGGQIYFGEHIFNSGVMLINNRLffKQEEVRKQLIEMTNELHDKVAQSDQSILNLLFKDRffLALDFKY NCITLHTHFSDYRPESGTYPPIIHYLTERKPWGLYECSIYRDVffffYYNAQDWSDMSQVTPSLTKDQVSQYTGVQY SALVYTFSSDLRNMGYLIENLPDVKFYVAAPVMVADSITDLLAYPNVSVLSDIAGQPPLIDSLVEGCDFLLDINA DIEVDGIIERFRQAGKPVFAFESVVHGEQGQFLYDQAHPEEMVLAIEAYCQNGELPVKKFQSYPKVLDIQQSLDY ILEHHTSVIRYGDGEMDIMMGHGIPYQDYDETLAEQLRSMIQLESSPELLVCLSDVFEGLERYNSESVNFWKKHL EHYKDAYQQYCTASFYGSTFISRPYMDLKDKTASVAHFEKLKQLffDERDILIVEGENSRSGVGNDLFDNAQSVER IICPSRNAYSKVQVIQEAVEKYADGKLVFLMLGPTAKVLAYHLSQKGIQAIDLGHVDSEYEWFKMGATSKVKFSH KHTAEHNFDQEIQFVEDEIYNKQVVVRI(SEQ ID NO 991)>orf02545MTDKASKKAIVLGADSNYMDKVETTIKSVCSHNRDIRFYIFNSDFPTEWFQLMNKRLSVLNSEIINIKI TDDTISHFHLPTPHLSSATYLRYFIPNFVFEKKVLYLDSDIVVTSSLTALFDIDLDGYPLGVVPDIPTTDEEFNSGV LLIDTNRWREEDIYRQLFELTIAHHEHVY⑶QGIFNILFKDRWKRLDITYNLQVGVDAHRYYMGDYDWYELFEGVPC IIHYTTENKPWKHFRFNRFRDVWWFYYGLNWNDILLRTHVLKETFLELISPISKHVSIFTNTCDIESIGYLLEKLPD VQFHIVAPTYFSPNVIELQRYSNCYIYPCADPKMKQDIIDKTDICLDINYGPAMDQMLQEMVRRGKTIYSFDCTNHF FNGESTVFTVDEIDELIRSVKELKM(SEQ ID NO 992)>orf02546LKDLVSVVIPVYNVENYLEECIQSVLNQTYTNLDIVLVNDGSTDASAEICARFAEIDGRVRVFHTENRG AALSKNFGVTQALGEYVLFVDSDDIAEKRMVETLYRQVEETGADIVIGNYFLYDENDGQYKLYVLERDFCIEELSAQ ELIDRQAGKWHLNASAFIMPVFKLFKKDLLLQVPLLMVGALMMKQRFIDCS (SEQ ID NO 993)[2422]>orf02550MRGGVDTTQVMTETVEDKVSHSITGLDILKGIAAVGAVISGTVATQTKVFTNESAVLEKTVEKTDALAT NGTVVLGTISTSNSASSTSLSASESASTSASESASTSASTSASTSASESASTSASTSISASSTVVGSQTAAATEATA KKVEEDRKKPASDYVASVTNVNLQSYAKRRKRSVDSIEQLLASIKNAAVFSGNTIVNGAPAINASLNIAKSETKVYT GTGKDSFYNIPIYYQLTVINDGSKLTFTYTVTYVNPKTKTLGNISKKMSNGYSIYNTGTSIQTMLTLGSGLGKPSGV KNSITDKNGKQVRPYNTSTMTMWRSGYTWANGAQMNGFFAKKGYGLTSSWTVPITGTDTSFTFTPYAAKTDRIGTNY FNGTRKVVESSTTSQSLSQSKSLSVSASQSASASASTSASASASTSTSASTLASTSASTSASTSASTSASTSASTSA STSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSAS TSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSAST SASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTS ASTSASTSTSTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSTSTSA STSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSAS TSASTSASTSASTSASTSASTSASTSASTSASTSASASASTSASTSASASASTSASTSASASASTSASTSASTSAST SASTSASTSASTSASASASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTS ASTSASTSASTSASASTSASASASTSASASESASTSASASASTSASVSTSESTSTSGSTNSRPQETITNSRQELPNT GEKQSVKSGLLGLILGLTGLGLVAKRRKRDDED (SEQ ID NO 994)>orf02551LKAFVEAHPDAFLREIAARFDCALPSVWAVLKQIKVILKKTTSFKEQKPEKVSEFLDILDNLKDLPVLY IDETGINRYLYRPYAGAPRGEKVYDKISGRRFERTNEVEQKLNGSFLIRYIDSQIRE (SEQ ID NO 995)>orf02552MAYSTDFKQGALDSIKEGHRHVEAAKVFDVGVRTLFTWEKKDVNKGT(SEQ ID NO 996)>orf02559MKIKEQTRKLAAGCSKQCFEVVDETDEVSLKHCFEVADRTDEVSNHTYDKVKLTWFEEIFEEYHTKKPC SSR (SEQ ID NO 997)>orf02561MKKSDVLDLIKYHYEGRETEFRNQSIAIARNFNKHGDTQIAQYIMGLMSQSDRFMPQIENPSEYLTPAK LDIGPLPLPLSIMNDLKGIINAVNHHIGINKFLFVGSPGTGKTESVKQVARLIGKELLVVDFSHLVDSKLGQTVKNL ATLFNEINNLPFKQNYIILFDEIDSIVLDRVNQNDLREMGRVTSAFLKELDRLSPEIVLIATTNLFENLDKAVTRRF DAIIDFDRYTDEDKVEVATIILNELLKQFKNVARDLKLFKKIINSANVIPNPGDLRNSIRTSLAFSDPSDPHDYQKR LLRSLHNGRNLSISKLSKLGFTVREIEILTGISKSSVSRELSED(SEQ ID NO 998)>orf02597MRFIVGIFISFSPEIEFLSSLKFLTDFVEICLLWQVMTP (SEQ ID NO 999)>orf02598VVEIIYFLIIIIASGLGSISGMGGGIIIKPLMDSFGYHSVSDIAFYSSFSVFIMAIISTTKRFSQSKEI KWRLIFTVSFSSVLGGFLGHLIFQVLLSQLSVRLVSIVQMILLFVMLLVSFVLTDFKKTYQFDKIGFYMICGLLLGL ISSFLGIGGGPLNVSLLMVFFSISIKEATMYSLAIIFFSQLSHLATIVVVTGLNQYHLAPVPVIFLASICGGVLGTV VSKVLPENWVRYCFKGMLFFVMGMTLYNLFHIL (SEQ ID NO : 1000)>orf02599MMGTNSEEGFLDDFEGPQVAVSVKDFSIADTPVTNQEFAQFVKETGYKTLAERQEWSFVFILFVPEAEREGYPHPAGAPffffLQVSNACWKHPYGENSNLVGLEDHPVVYVALEDALAFCNWSGMSLPTEAQWEYAARGGRQSEYPff GDTLLEGGYYHANTWQGRFPYENTALDGFIGTAPVYEFLPNDFGLYQMIGNVWEWCRNPRYTLLASFNEDDYELPKY GIQDEEYAIRGGSFLCHCSYCNRYRVAARNGCISTSTSSHLGFRCLKE (SEQ ID NO: 1001)>orf02602 [2439]MVQTKQPNIILIVVDQMRADALSLNSKDKLVSTPTLDMMASVGYNFENAYSPVPSCVPARAALLTGLDQ DKSGRVGYQDEVPWNFTNTLPKVFKDMGYQTECIGKMHVFPSRQRLGFDHVLLHDGYLHVDRKYDKAYGSQFDYASD YLAFLKGKVGYDVDLIDDGMDCNSWEARPWDKDEKLHPTNWVVSESISFLQRRDPTVPFFLKMSFEKPHAPLNPPKY YFDIYMERLPQFLDLHIGNWEVLEKQIPSIYALRGKLKEDDQRRMVAAYFGLITHIDHQISRFLTALKEFRHDKDTI IWFVSDH⑶QLGEHYLFRKGYPYQGSIHIPSFIYDPAGLIAGNRGTIKQLVKIQDIFPSLVDLAGGTTTDELDGRSV KNLLFGQYEGWRTEFHGEHALGKDSSQYILTDQWKFIWFPVLNHYQLFDMKKDPHEMNDLYPSEKYQPIVRQMKKKL VDFLRYREEGFWDEELVPVELSKITPTLTKTCDSQS (SEQ ID NO: 1002)>orf02604MNTMLDKMQEKLSPIAMKVENQKFLVALRDSFVGTMPVIMTGSIALLLNAFLVDLPQQFHLESITKTF QWLVDINNLVFKGSIPIVSLLFIYCLGVNIAKIYKVDTVSAGLVSLASFVISIGSTVTKSFPLANV⑶VKLDQILQ GIDNLAFDGKNLMVTIGNVIPGNHINARGYFTAMMIGFLASIIFCKVMKKNWVIKLPDSVPPAIAKPFTSIIPGFMA MYIVAILTYVFHLLSNDLLIDWVYKVLQTPLLGLSQSFFAVILMIFLNKLFWFFGLHGGNVLAPIMEGLFGVAMLAN LDAFQKGEPIPYIffTSGSFGAFVffFGGLGLVLAILIFSRNSHYRKVAKLGLAPVLFNIGEPVNYGLPWLNPLLFI PFVLSPVFMATVAYWATSWGLVSPVTQNVTWVMPPILYGFFSTAFDffRAIILSWCLIISVLTYFPFVKMADKTELS (SEQ ID NO 1003)>orf02605MNESNLESVMGLIMYGGEAKSNAMEAIQAAKK⑶FSKANRRLADANAALLQAHKAQTEMLTREAQGEKT SISLLMVHAQDHLMTSLTFVDLAKEVVEVYERFEKN(SEQ ID NO: 1004)>orf02606MAKVTIMLACAAGMSTSLLVTKMQKAAEDKGLDAEIFAVPAPEAEEIVATKEVNVLLLGPQVRYLLCiDF QEKLKDRQIPVAVIPMTDYGMMNGSKVLDLAESLLD(SEQ ID NO: 1005)>orf02607MKRLISANPSEILQMNAEELKQSI LASEGRWLSENWTRETFViiD ITNSEIARAFGADMILLNCVDV FEPKIYALDSSGDDVIHRLHQLVACPIGVNLEPIDPSAKMLEETQEIVAGRVASVETLNRIEELGFDFVCLTGNPG
tgvsnreiikavqtakenfsgliiagkmhgagvnepvaelsvaeqlleagadvilvpavgtvpafhdqelrevvd
LVHSKGGLVLSAIGTSQETSDTDTIKEIALRNKICGVDIQHIGDAGYGGLATVDNIYALSKAIRGVRHTVSRLAR SVNR(SEQ ID NO 1006)>orf02608MEKLLQEKLLPVAARLGNNKALVSIRDGITLTIPLLLIGSLLMVIASFPIPGWEKYL⑶IGVADYLWKG VDSSFGLLGLVASFGIAYFMARQYKVDGIPAGIVSLSSFITVTPFIRGEAGAGMPTAFMASKGLFVAMILGLINGYI YQWFINHNIQIKMPDGVPPAVSKSFSAIIPGAVTIVGWLIVYATLDKLSLPNLHEIAQVALGGPLGLLGNNVIGLLI LIFLNSSFWFVGLHGGNVVNAVMKPLWLANLDANKVAYQTGETLPNIFTSVFMDNFVFIGGGGATIGLVLALGYLAH KKKASKQLKTLAPITVIPGLFNINEPAMFGVPIVLNILLLVPFILAPMFNLLVAWGAMASGLVPLTYTDPGWTMPPV ISGLLATGSISGSLLQIVLIVLDVLLYLPFVIAIEKRFKLLED(SEQ ID NO: 1007)>orf02609[2451 ] MTLSKKQLQLRAKILETVYTLGPISRIEIATKTGITPATTSSITNDLIKENILLELGEDEHDTSVGRKK ILLDIQAKRFYYIGCELSEKHFTFAL⑶NLGNILKEEKEIVTKQLIQEKGNQLINQTLKQFLNNCSDYEIEAIGIAL PGRYLDDYKITTNNPLWQHIDLEMIQSHFDKPLFFSNNVNCMAIGKRLFSRQQNDPNFAYFHFARGMHCSYIYDGNI YGKGNLMIGEIGHTVVSSEGEECSCGRKGCLQTFAGESWLIKKSKILYHQSPYSLLPSLVKNADDIDIQVILTAYQL GDTGIITLIHQALLYLSQTILNISMMIDSQKIYLHSPLLTNQHIIQKLYSEMNYKPKLLYNRLPEVIIEPYNDFTAA HSAIALCLYHTILHS (SEQ ID NO: 1008)>orf02628MPFKENLICQHRNHHCSVFFISLGLLHNIHIEIDISQTRASFLDLSDYLQAVLMILQKFCQAIGLAQRL DLLQLHLLHLTRLLL (SEQ ID NO: 1009)>orf02636MYLLLLVVKDHIALIDKEMHVWRPNCILRDLTNFFIKRNHIVTHKTNGSTTKR(SEQ ID NO : 1010)>orf02637VLTLMNHFIKEIQGISINHLTILIKNSIFKLNLKNRIIG (SEQ ID NO : 1011)>orf02641MKIKEQTRKLAAGCSKPCFEVVDRTDEVSSKYCFEVVDRTDEVSSKHCFEVADRTDEVSNHTYGKATLT RFEEIFEEYKGVPR (SEQ ID NO 1012)>orf02655VCQRMDARTCKTTIIAVHNVLTALQQTffIAVQLYQTK (SEQ ID NO : 1013)>orf02656LHLGKSILSLPVKGKDLEFLVHLFVINHWIGSPSRTSTFCRCKVLNGME(SEQ ID NO : 1014)>orf02657LEQTVIIANNPCELYWDNHLSFLSDSLLKQVIVHLKRICLDIHHDRGCSHVRNDTT(SEQ ID NO: 1015)>orf02673MLEEGTKDQLAELTYPFGRGVNLSFGIKDVPKLYQKVMEANYPIYRLLTKRKFRVSDPYIYPHKFAVLD PDGYFLRFSE (SEQ ID NO 1016)>orf02689MIACRHDICKSQKGLEHPFCIIRRLTRDFNQRPVCIVEANIFCLKITPQIIT匪IVARTVKSSKTGITL TTSMCKRDNHKITWFHRRNGFPSFFNNPNRFVSTIFMSSFRFWITVPP(SEQ ID NO 1017)>orf02705MNMNKDQIAILNGADNLNLTLWITLKEICKEGCKSFFPVRNTCRMLDIGIPYRLGLSLSNSSVLNGMDV (SEQ ID NO 1018)>orf02725MHKLRIFVNQLCRRFGIILGPFLVLGFQVLTQELELAIFFDLREEVLLQVIPQVCHFCYLRKEFTTLNQ HELTSHDHVLTRHFQTHGLQG (SEQ ID NO: 1019)>orf02732MQVTIEADSGLFLLSPVVQLLKVEIDVKQVTMSLDNLGRTKLSHQTFWVAGVEVHVPFNNADALPKWRI RT (SEQ ID NO : 1020)>orf02734[2477]MKNGIDFAHIAITDFFHNQAIAMGIAHYNDGLLCHDGNTSKSFLTAKAR(SEQ ID NO : 1021)>orf02758MSIVKSHSFSISLGIFNSFffNNIHTSECFYFLCKGKSNRSNSTISVNQMVFFINIQRFYCFAIEDFCLL RI (SEQ ID NO 1022)>orf02759LNTLLPPDNLCLFTIYLTGFSCICINSYCHNFWEIFNQLFYQLS(SEQ ID NO : 1023)>orf02778MYNKVIMIGRLTSTPELHKTNNDKSVARATIAVNRRYKDQNGEREADFVNMVLWGRLAETLASYATKGS LISVDGELRTRRFEKNGQMNYVTEVLVTGFQLLESRAQRAMRENNAGLKGQIWXXIHSLIN(SEQ ID NO 1024) >orf02782MQFTRTTHHPKTLFTTKFAWENEIPFWHHGTRKSHNGFQPNTRIRCSCNDLHYLVTCDCNLADVEWTV WMSYHLDNFTNNKLRFLIINNFFCKTFRL (SEQ ID NO: 1025)>orf02784LTALCNFKQARNLKNVPSYCFPIFFEENTGYLAFAFHIQFGISAIFHDDHKDITDMFFVIRKNHCFLFL LFQSC (SEQ ID NO : 1026)>orf02788MKIKDQTRKLAAGCSKHCFEVVDRTDEVSSKHCFEVVDEADVV (SEQ ID NO : 1027)>orf02789 MYYSVDDVVSNAFKKRMILDSFFAFNCSGTMKVSTWVYDKGEWYYVSSSGSMIANDWVKDNGK(SEQ ID NO 1028)>orf02793LTWILTKIARKDSLQLFELEANLISFLLVMSVDLAPFCFKEENF (SEQ ID NO : 1029)>orf02803MEDIDEDELLIFEKVLGQLQANIKGIGGENKEISQKN (SEQ ID NO : 1030)>orf02804LHLRTCFVRQTNKLSPLINRTRLQFHQTILHYTLNQITSNRLGNIEFLLDIFNQDQVLVFLAIIQKTHN LTLRPTHKFNAATFGFLLHHQVNLMTKTLKD (SEQ ID NO : 1031)>orf02821MLEIWKYRPFVSEFWNDFKNNHDKQFVDPISLYLTLKDDDDPRIEEESEALENMILQYLGEDDAS (SEQ ID NO 1032)>orf02823MQDLLFHFYSYRLNLTFFFFELLICLLNSEFDLSKFIFVYFDEYFHEDSLKMNLHQFSFSF (SEQ ID NO 1033)>orf02829MAFNQFNRCIGLSIPTAPNVPGTIINRSYLHDATVPNNVREKT (SEQ ID NO : 1034)>orf02845LTDFHDFKFIFFENLFKSRQLYLQSQNSVLSNLffLAT (SEQ ID NO : 1035)>orf02850MKKLFILISNLLASLFFVWVFTIWTDTYVSHYYPNVVVHDSSPETTFQHVATRLEKLAEETDSFIAIQHQDPNSEGTTVFSYTTFGDGKLPDGLQEKNLEDAQSSSVETNYFVFDGHLDIHLLREELSQLGLTNMHLTIPSKLSTL MAIFSNGFQLISLLIFILTFVALTLISQISQLRSSGIRLISGEKRWSIFLRPVGEDLKAIAVGFSLAGVLAILMQKI LSLPTQSLMTIGAGLLSYNLILLSISLFFAQLFAVGIKKIHLMQIIKGQVPVRGIISLILIGQLLAIIIVTLGIGSS LKYSQAWQQHRIGQEIWSQERQLITLSISREGTSPGFDEQAQRKLRTWYQLMDLAVSEQKAFLSRHQLIDRTLQNGM ASSKNLITSTEffHDYNPNGNVLIVTPQYLERQNIPVDTTIEQKMNHLNVGEFVLLLPEHLRSEEEHYKSVFEDDLTS RMSSQDERQQMTATVGYLESGQDRFVYNTTPISYQQFLKDPIIIVITPQSTGPQSILFffIDAVQNYVLFNQLSDAQE LIQRQGIENWVSEMQTGYHNYITLLDNIQRERWVMLAGAVLGIATSILLFNTMNRLYFEEFRRAIFIKRIAGLRFLE IHRTYLFAQLGVFLLGFVASVFLQVEIGVAFLVLLLFTGLSLLQLHVQMQKENKMSMLVLKGG (SEQ ID NO 1036)>orf02859VLKWCILRINHHISRKVDNFLEGTRAHIKGQAHTAWNPLEVPDVRYRSFQFDMSHTLTTNFRTRYFNPT AVTNNSSVTNAFVLTTSTFPVFCRTKDHFIKESFTFWFQGTIINCFRFFDFSIRP (SEQ ID NO : 1037)>orf02869MPWKELCHKLAPKVFKVIRIYSRENKKSPSNWAFCSFET (SEQ ID NO : 1038)>orf02877VDSLFLSLGEESNQEINLQESFSSTDCNPTLISPETTVAQGLCQDIIYRPFT(SEQ ID NO : 1039)>orf02880VNPKSLGSFFLQDSKGFKELVLGHAKLSLPRIVHNVCPQFKNASRIITTRDDFWNACYSLQMFNIFKGI QVNGRTQFTCIGVFLVWRVVGREHNLRTQKVQFMAHQKLYITRAVHTTTFFLENFQNSWSffSSLNCKIFLKALVPRK SLVDGSCLLTNPLLIIQVKGSRELGNNRF(SEQ ID NO : 1040)>orf02884MDNLCFHNAWTDWASILKQAVVTEDDMTKQNDFFLGIIDAEFHNCLGNFAINESDMSKKITSHCVLCLV WPRQLDDLS (SEQ ID NO : 1041)>orf02885MQHNPRIEQALIELRINFANSVCQTHHGRRMIGQARFKGMVVGLGSWIGVEFLIILGVEISDNPLPDRI FNFENHLRHVVTNFLDINW (SEQ ID NO: 1042)>orf02886LIDLRGIVINFSASFHVDNLTCGKGLNVMRLGIPELPINLATIILEGKG(SEQ ID NO : 1043)>orf02899MDALVLQKNQETIQQIAVKIRFLDGHDYYSLIDIDNRRTNQTVFPFVNF (SEQ ID NO : 1044)>orf02900MAFFTEIPTRACLINLAITLHIVETCQGFNDLSLHLRVLAL (SEQ ID NO : 1045)>orf02904MLLPLPFNTSKIKQIAMHSDLNQKEMIGHIFHDEDIF (SEQ ID NO : 1046)>orf02909MKQTVKKLALVASIAATLGGGVSVASAAVQYPEGGVWTYGSGNGGAYSNYYHPSKYHSSTVVSRKTGSS DKGYAGAGGTSRAffIRTSffGEKVAFYYNV (SEQ ID NO: 1047)>orf02919MNQENLFLLQEIKDKLLIIIDTVHIAVDFffEDIEPRLGFNGRQTffNILNGIIDEISLLVDSSTRKKQFID (SEQ ID NO 1048)>orf02920 [2533]LLGQNVRAKAHIGQHIEPFDIAL匪SLRARQDHPTHTETCYAVGF (SEQ ID NO : 1049)>orf02921MSVHYHAVIDFIRKDNQIVLTGNLNNLQQEFLRIKGSSWVIWIDKDDCLGIGSDF(SEQ ID NO: 1050)>orf02923VTYNRIRQTSHPLCNQKCQQQ⑶AYNPDSLVNKNSFDITILITNCLHDTYFLGTLHDIDVNNDTNHNRC YHNSL (SEQ ID NO : 1051)>orf02924LIRQHETVAVLHVIFIIDYTYNLRLKLSNLTSFGSTFYNAG (SEQ ID NO : 1052)>orf02954LHTSFRSSVGHSHTffHQDIVRPILFSRFNDSIVILffQNCPTFN (SEQ ID NO : 1053)>orf02968LRLAKLVPSLKIALKSFSLFTRKFFFKTQLHLLNYYYYTIFFKKANHSKVLDNFIRKRSWKNNFPNSLY (SEQ ID NO 1054)>orf02973LKAEQQAIKNIQFLEQDLPKNPLEKEFDCLAVSRVLHHMPDLDADLSLFHQHLKEDGKLIIADFTKTEA NHHGFDLAELENKLIEHGFSSVHSQILYSAEDLFQGNHSEFFLTVSQKSLA(SEQ ID NO 1055)>orf02974MKHDFNHKAETFDSPKNIFLANLVCQAVEKQIDILSDKVILDFGGGTGLLALPLAKQAKSVTLVDISEK MLE (SEQ ID NO : 1056)>orf02978MVDLQSFFTRKYLNLNSVDAYLILPRLQGHLSYPQDFFLLQDFCFLLPIFLNLSQKEGRNAGKDS (SEQ ID NO 1057)>orf02991VTENPAPFVFTVSINSFFTVVAFTTGTDARNQDLVTFFEVGNSFPNFFNNPNPFVAKNGTTLASRNIPF DNMEVCSTNSGFYNTHNSICWLANNWFVYINKRSKSffFNIRXXIPFIN(SEQ ID NO: 1058)>orf02993MRIRNSPFDHILQTIFEFEDRTCQVTCRFEACSSICNDNWEFSQHIISVFQSPSCHTVCDKSDVFCSF LFDKNFASLWIYVVTITDQLCIGMWQLVHGSNHTQFTVSQPTHSIVSMHPNTRSSIDCFFGFIKSRV (SEQ ID NO 1059)>orf02994MSKSNRHTFARNCTNKVFHPITFffCKGNFIKQAICRFLPRMKLLNTRVSHISffILCPLKSFCEIffTFII NPTNLSTCCFFIMVSKIFSDCKQLLISGC (SEQ ID NO: 1060)>orf02996MQCTFNVWHHIYTCISM 匪 SIHKSWGNAITCIVNHLSPFRNLLYMFPKLAVHKFQVTTSTNSVWVEKL IRFNIVRHNVNLLKRLILQFIMSITL (SEQ ID NO 1061)>orf03011[2559]MTLHQTFRFQNLEMPCQSSLINFQTLLNRHLVTRRMLQQKQ (SEQ ID NO 1062)>orf03023LLSSFQDAVKFFAVVFFRKVQPSQEVAPNASSFTDQFMGG (SEQ ID NO : 1063)>orf03025MVVTTFNDFSIFKDNNLICIENGFQAVGNDETSSTCYNHLHGMLNLAFRHRIYV(SEQ ID NO: 1064)>orf03031MAEFNSVITTVTGI⑶RLGAVILAEIRNIHAFDNPAQLQAFAGLDSSIYQSDQIDLAGRMVKRSSPHLR (SEQ ID NO 1065)>orf03041MQQYVDIKKQYPDAFLLFRMGDFYELFYEDAVNAAQILEISLT SRNKNADNPIPMAGVPYHSAQQYIDV LIEQGYKVAIAEQMEDPKQAVGVVKREVVQVITPGTVVDSSKPDSQNNFLVSIDREGNQFGLAYMDLVTGDFYVTGL LDFTLVCGEIRNLKAREVVLGYDLSEEEEQILSRQMNLVLSYEKESFEDLHLLDLRLATVEQTASSKLLQYVHRTQM RELNHLKPVIRYEIKDFLQMDYATKASLDLVENARSGKKQGSLFWLLDETKTAMGMRLLRSWIHRPLIDKERIVQRQ EVVQVFLDHFFERSDLTDSLKGVYDIERLASRVSFGKTNPKDLLQLATTLSSVPRIRAILEGMEQPTLAYLIAQLDA IPELESLISAAIAPEAPHVITDGGIIRTGFDETLDKYRCVLREGTSWIAEIEAKERENSGISTLKIDYNKKDGYYFH VTNSQLGNVPAHFFRKATLKNSERFGTEELARIEGDMLEAREKSANLEYEIFMRIREEVGKYIQRLQALAQGIATVD VLQSLAWAETQHLIRPEF⑶DSQIDIRKGRHAVVEKVMGAQTYIPNTIQMAEDTSIQLVTGP匪SGKSTYMRQLAM TAVMAQLGSYVPAESAHLPIFDAIFTRIGAADDLVSGQSTFMVEMMEANNAISHATKNSLILFDELGRGTATYDGMA LAQSIIEYIHEHIGAKTLFATHYHELTSLESSLQHLVNVHVATLEQDGQVTFLHKIEPGPADKSYGIHVAKIAGLPA DLLARADKILTQLENQGTESPPPMRQTSAVTEQISLFDRAEEHPILAELAKLDVY匪TPMQVMNVLVELKQKL(SEQ ID NO 1066)>orf03051LTNLSSVDSEELFQFYRERGNAENFIKERKAGFFGDKTDSSTMIKNEVRMMMGCLAYNLYLFLKQLA GDEVKALTIKRFRRLFLHIAGKYVSTARRHILKFSSLYAYSKQFQALFDTICQINLILPVPYRARGQGKTCLTE (SEQ ID NO 1067)>orf03061LFDDRQAINICPPTNGSLRLTSLQVDQNPCPPSTNLNKILARSQFLNHIQQISLSLELLQANLWNLV (SEQ ID NO 1068)>orf03092MKIKVQTRKLAAGCSKHCFEVVDRTDEVSSKHGFEVADRTDEVSSKHGFEVADRTDEVSNIYTVRRR(SEQ ID NO 1069)>orf03093MDFFNYLLWMICHNHGLHTLLLSKDCVCHTARDKDGNHRIKSVFPTKGQTCYQHDSSIYQERNTTDILT RFLTNSQADDVRPTTCDIVSKSKTNPQTHNNTPKKGIDNGILCQGCHRDKLDKEGTHRYRDKGKDGELMANLIPS (SEQ ID NO 1070)>orf03104MIKQIKAHLNKSIQSIIGQKVEFVKQDEQAFTRKRRLSLETMIRTILGMGGKSLSKELLDARLTVSNSA LVQRRYQIKPEAFYALFKEFTAPIPLNTDFPIFAADGSDICIPRNPMDTETSIQTQTDVKSYNLIHINALYDLTTGVYRDVSIQDKHAQHERLALIQMMEASPFRESSCYHG (SEQ ID NO : 1071)>orf03108MAHFQEKGWLYIIRIRDGKQSMPSSFNLPNTECFDQKVSLKLSRKQTNQLKKLYRDFPNDYHFIPHNSI FDFLPETSRKQDPVTLYELPFRMVRLKVEEGKYETLVTNTDYSVQELKNLYASRWGIETSFRDLKYSIGLVNFHAKK KEGILQEIFARFTNFNFCRWVTSQVAIDSSHKKQRYKVCFSDAAYACRLFFNGSLSSHQLKNYLKKQLSIIRPNRKY SRKIKAQSVVDFICRVT(SEQ ID NO : 1072)>orf03110MCELDILHDSLYQFCPELHLKRLNSLTLACHALLDCKTLTLTELGRNLPTKARTKHNIKRIDRLLGNRH LHKERLAVYRffHASFICSGNTMPIVLVDffSDIREQKRLMVLRASVALHGRSVTLYEKAFPLSEQCSKKAHDQFLADL ASILPSNTTPLIVSDAGFKVPWYKSVEKLGWYWVSRVREKVQYAP (SEQ ID NO: 1073) [2582]>orf03139LSIQVETLELRVIFKEIKEIVKQFHQLHTMAFKRQVPLTIPVTM(SEQ ID NO : 1074)>orf03154MGALGYYEGFVPYVSNQYKNQAEEEGKPLSDKYIFEKILGKTYAAFKKDQINERVEKLGKLKPITINYN GKSEVIDSKEKLQELMNKAVKDEVAQIS (SEQ ID NO : 1075)>orf03155MMGDGMKEFQFERKQRFSLRKYAIGACSVLLGTSLFFAGMGAQPVQDTETSSALISSHYLDEQDLSEKL KSELQffFELENKLLNLffEH (SEQ ID NO: 1076)>orf03159VNITKTSIIKAHTTKEDGIDHTFTRFNIMSIFYSTRKIFLDKLNSTNRQFLGYIISTRCYQSFNSVSQS IHTSSSSQAFRFGKHEFRVINRDKSKAILVNHYHLNLAFFISNHIVNSDFCRSSCRCIDSHNWQAFFSRLMKPFIIL WFSTICSHDRNTTSCILWRTPAKTDDKVTAMFLQSSYPICDIFTSRVWLYIAKDDIFDSFCIQWF (SEQ ID NO 1077)>orf03175MSMDNCIDIITSLILNQMHIPFARWQAFSLYNISINIHHYNIGFFDFKEINTRRGNCHQLFFTIENAEI PTCSFRQICFY (SEQ ID NO : 1078)>orf03182MNIAIRIILNFFRVMGNHQNSLAMMMGAVVHEFVKFIFTSCIHPRCRLV(SEQ ID NO : 1079)>orf03183MLLIMSIQTTEPAFSRIATRLDKFIDRTWKTSIKTGNLLRKIGYSQFLTLRICL(SEQ ID NO: 1080)>orf03184LQNSKTSLDERRLSRSIFPSQGNKFPTINTIIDMFKNRLLIIIEGQILYRNISHYLISPTKAVKNR (SEQ ID NO 1081)>orf03197MSNSFVKLLVSQLFANLADIFFRVTIIANIYIISKSVIATSLVPILIGISSFVASLLVPLVTKRLALNR VLSLSQFGKTILLAILVGMFTVMQSVAPLVTYLFVVAISILDGFAAPVSYAIVPRYATDLGKANSALSMTGEAVQLI GffGLGGLLFATIGLLPTTFIILVLYIISSFLMLFLPNAEVEVLESETNLEILLKGffKLVARNPRLRLFVSANLLEIF SNTIffVSSIILVFVTELLNKTESYWGYSNTAYSIGIIISGLIAFRLSEKFLAAKffESILFPLVAMAIVTLTILYFPNAQMFLLFSALVGMLSQLKEVPESVFLQETVEENHLVNVYSVLEVISTLAFSVFVLLMSYITESFGISISFWLSAICL MIEAILIYIRRDYFK (SEQ ID NO : 1082)>orf03198MSKLLDKILSRE匪LEAYNQVKSNKGSAGIDGMTIEEMDNYLRQNWRLTKELIKQRKYKPQPVLKVEIP KPDGGIRQLGIPTVMDRMIQQAIVQVMSPICEPHFSDTSYDFRPNRSCEKAIMKLLEYLNDGYEWIVDIDLEKFFDT VPQDRLMSLVHNIIED⑶TESLIRKYLHSGVIINGQRYKTLVGTPQGGNLSPLLSNIMLNELDKELEKRGLRFVRYA DDCVITVGSEAASKRVMYSVSRFIEKRLGLKV匪TKRVEISRFWVLEIIRWLEKPSTSR (SEQ ID NO : 1083)>orf03202MFLRCATFKLADSRLNIFTCFFFGEIRFNSRNQVVKAFITDGTVISTIIVRGTVPCNQffTKTCPAAFDI INGDVGFffKAVVDNAK (SEQ ID NO: 1084)>orf03203 MLQITCVVCISCTKVSLVFTWENKDHTTVTQTCVKVNWL (SEQ ID NO : 1085)>orf03204LRSLIRQITYFITPRTCCINNQTGLDFKHLVCQEITSYNTCNLATFVKEEAFCLHVVGNEGTVLVGTFD VFNHETRIVVTEVKIHSTSYQAFLLQVWLAFQDLILAQNLVRSWCVAHTC(SEQ ID NO 1086)>orf03205LHFNQTSLKTASCRLQGYTSSCDSSTDNQEVQGAFLHFFN (SEQ ID NO : 1087)>orf03216LKIDHTQLSPSNLLNTFVTPFIFYLKHSINLTNAEIICFSFYFHADFLVHYPENQ(SEQ ID NO: 1088)>orf03224LKKVQHTQNVDFNKKLSRIKTKYLYGLKEKSEAELTLKTKETKEELTAAFEQFKKDTLKSGKKVAEAEK KAKAQKEEDRRNYPTNTYKTIELEIAEAEVGVAKAELELEFAQAQVQIPQDTEKINAAKSKVEAAKSNVKKLEKIKS DIEKTYLYKLDNSTKETPKSRVRRNSPQVGDSRELKETIDKAKETLSTYMVTRLTKLDPSVFWFADLLMDAKKVVEE YKTKLEDASDKKSVEDLRKEAEGKIESLIVTHQNREKENQPAPQPGGQAGGSMVVPPVTQTPPSTSQSPGQKATEAE KKKLQDLIRQFQEALNKLDDETKTVPDGAKLTGEAGKAYNETRTYAKEVVDKSKKLLSQTAVTMDELAMQLTKLNDA MSKLKEAKAKLVPEVKPQPENPEPKPQPEGEKPSVPDINQEKEKAKLAIATYMSKILDDIKKHHLKKEKHHQIVALI KDLDKLKKQALSEIDNVNTKVEIENTVHKVFADMDTVVTKFQKGLIQNTPQVPEAPKSPEVPKVSDTPKAPDTPQVP EAPKSPEVPKVPEAPKAPDTPQVPEAPKSPEVPKVPDTPKAPDTPQVPEAPKSPEVPKVPDTPKAPDTPQVPEAPKA PDTPQIPEAPAPETPKTGWKQENGMWYFYNTDGSMATGWLEYNGSffYYLNANGAMATGffLEYNGSffYYLNTNGAMET GffLEYNGSffYYLNTNGAMETGffLEYNGSffYYLNTNGAMETGffLEYNGSffYYLNTNGAMETGffLEYNGSffYYLNTNGA METGWLEYNGSffYYLNTNGAMETGWLEYNGSffYYLNANGSMATGffLKDGDTffYYLEASGAMKESQffFKVSDKffYYVN GSGALAVNTTVGGYRVNANGKffVN (SEQ ID NO: 1089)>orf03230MDREILKFFQDLLSILSHNDMITLFCQKCCNSFSNHFLVICN (SEQ ID NO : 1090)>orf03232MFITLRRICLRACVVEKEQSYLKFLFFQKRPVSFLHVKSVLAGI(SEQ ID NO: 1091)>orf03233MVKTTNRLEAIGFSFILFENLFKPRQLYLQPQTSVLSNLRLAA(SEQ ID NO : 1092)[2620]>orf03239[2621]MTRKLNPSYTNVASATTLTFNQVASTFRKACLDHVVNLTRNNLKGICQLTPLQLHDTRLI(SEQ ID NO 1093)>orf03270MRTFFLYSSAFKKHSSPSPINDGLYHLLLQSLYNILELIHDIFQSLKGFILKSTFTNLFPHLFNGVHLff CVffRNKCKANISRNL (SEQ ID NO: 1094)>orf03277LVSVFYSLLQVDNVDSVTFSKDVLSHLRIPATSLVTKVYTSLKKLFH(SEQ ID NO : 1095)>orf03286LIVWILKNHTDLTTYIPNIFLSQTLAINYNLSRFCFQ (SEQ ID NO : 1096)>orf03287MPYNRKPFSTFHVKRNILHIVVVLIFFITKRKIFYINY (SEQ ID NO : 1097)>orf03291MFKKMSNSSRILFYISVNFCDKRIYRTKLYSDTPVNLFKFLFRQKSNCQSIGQTSSINLFFYSWIVFFF KNNLCHSIPSIK (SEQ ID NO : 1098)>orf03304LADGSGKLAEGGTKLTSGLEDLQTGLASLGQGLGNASDQLKSVSTESKNAEILSNPLNLSKTDNDQVPV NGIAIAPYMISVALFFAAIS MIFAKLPSGRHPESRWAWLKS(SEQ ID NO: 1099)>orf03310MKNTVKLEQFVALKEKDLQKIKGGEMRLSKFFRDFILQRKK (SEQ ID NO : 1100)>orf03330LVEQLTFNQWVTGSSPVRVIYAGLAELADAPDLGSGA (SEQ ID NO : 1101)>orf03344MKIKEQTRKLAAGCSKHCFEVVDETDEVSNHTYGKVKLTWFEEIFE (SEQ ID NO : 1102)>orf03352LIDVLFINSFIGRICFYCYRRIHATCLFLQLFSIVILNVAHTLKHSIFIVITFISRCRNFIIVRILLEN QFSRNQGIDNRVGQSRY (SEQ ID NO: 1103)>orf03353MVNVNQVSIEVKNTFKNWNFTSSIELTTFSKFSQSPTMT (SEQ ID NO : 1104)>orf03364MGFSMKLIHDLDMHTTHSTAKMLYNVKAIKNDFSIRE (SEQ ID NO : 1105)>orf03368LKSVGSRVEDKRYQETIVATFSDILKRSREMQDQNIKXXFIH (SEQ ID NO : 1106)>orf03372MLTIEPTKAPLVNVCDTANTARIDDEPYSP⑶FXXHSIH (SEQ ID NO : 1107)>orf03373 MRWNIGCHPNRDTSCSINQKVWKTRWQDQGFPFIGIIVINEINCIFVDITKHFQSNLAHTCLGITLSGS TISIHGTKIPMTIYKHVTVAPPLSHTDHGFINRGIPVffVIFTHDIPCNTSRFFMGFVffGHTQFIHSVKNATVNRF (SEQ ID NO 1108)[2652]>orf03380mtdfntflqlsegwslfrsdfllcikhflnsfssskgqlkasptrcnldnrlvvll(seq id no: 1109)>orf03390mggnppmkkysivdkivlstkikriiiftvfrenwepymkkytevfqsqfpnlnidyllldteqidlds
yldadiiiigggntekyiatyvnqefknyidhmlnkgakvigfsagalllgekvyvspndnsdhqikikdglglfsq
flisvyydswndkankdraeelvnvpiiplndhsclvldklgniiekid (seq id no 1110)>orf03393myggeaksnameaiqaakk⑶fskanrrladanaallqahkaqtemltreaqgektsisllmvhaqdhl mtsltfvdlakevvevyerfekn (seq id no 1111)>orf03396mlarskncfmkslsifllifyffdsyqiskkrrsligl (seq id no 1112)>orf03399vtahrifgtssihskliglamlgitamkiichklnrnhinifrrlgiqgktefllihlirqvkmnhlsq gmnpticptstvnsnglpfi (seq id no: 1113)>orf03402mlkngiiswkdfksffcqgcqtshcykpmqavqgigsqis (seq id no 1114)>orf03403mrfladqdriqhhryswalfdkvqgllshadsrektnlnspkfhitqai(seq id no :1115)>orf03405msygrpyilnvdgaihdgwlaisnyenslnkdylfyilssnvvysqflslisgavvknlnsdkvasili plpplaeqqriieaiesalekvdeyaesynrleqldkefpdklkksilqyamqgklveqdpndesvevllekiraek qklfeegkikkkdldisivsq⑶dnsyyeevpceipeswewvrlnditsyiqrgkspkysnipiypviaqkcnqwsg fsidlarfidpetvhsyqkerllrdgdlmwnstglgtlgrlaiyhenknpyvwavadshvtvirvlsgvinchfiyn flsspivqsvieekasgstkqkelltktikeyliplpplpeqsrivdrieqffahidali(seq id no :1116)>orf03424laqisilhfdflsidkhshtvfntlrkslqttlalsatskqcfeqlaasflvcslifieykv (seq id no 1117)>orf03430mgfkvshfkipsshlsinvlrtvenfteigqgllhisp (seq id no 1118)>orf03431vgffdfgltnscrqvrqftqtvqdflvcchqgivkegqgyagicfkfhpslgnigkfviaivrrlrhks ivanmahlnvdlfqfrkglleilksvkialvitaklvdvfasfldctqeiltvlv (seq id no 1119)>orf03439mnityivgngldlqyglktryrdfyefqnkvyisrteneekysnfiyeslfsdkvndyenwsdfelsig kltkdndlisssieikekfiddfsevvddlreylriqqeknlekgnaidfistlddmrtslpvinqpaidkkynenp hqddivnivtlnythvidklyngsaksfrnqlranlynfyieppihahgtvdvctvlgvsdeiqisnsfdeeqkesl iknlvlknyrenmdvknsdiiknsdiiilygvslgetdgyiwnqiaeqsirssvpviiyhyvphfdagnptrvkrly rnvedkfiqnsgidlelekklrdnlivvigktifnlmer(seq id no: 1120)[2676]>orf03440VGAKFNDEKTKHIVTHYISRDALNKTITVLSKIIEVFEEHFDRAITCEMFSDSSTFASINFSEYGISKS KFQQYLRDSCFIENFGVEHTTVSDIQNSIVTFYDVHTDIFRLLNKLNIDISEANIMNQTTVLLDEKNIELLLSKAPY LVSMIVEDFSKLSVDDFSLDNNDLKINLPSPMNEPVVGVIDTLFDKRVYFNEWVEYHDFVSPDISKDSQDYKHGTAV TSLIVDGANLNPNLDDGCGNFRVRHFGVSLQSGFNSFTIIKQIKEIVSQNADIKVWNLSLGSNDEIRENFISAEGAL LDEIQFENDVIFIIAGTNASVINGKRKRIGAPADSLNSIIVNSVDFNNQSVSYSREGIVLSFFVKPDVSYYGGGNGD FINVCEPLGLGRVAGTSFAAPFIARKMAYLIHIMGLSREEAKALLIDAAIPWNDKKTFTDLSLIGNGIVPIKMDDIL STPDDEIKFIVSDISRAYDTYNYDFPVPISSESYPYVAKATMCYFPNCSRKQGVDYTNTEMQLTFGRLKSDGIKSIN KDNQHAEDTPGYVRENAARNIFRKWDNVKHIGESFTSRKRAKAILNPSNPQWGMSIKTIERLKS⑶GQGVRFGVVVT LKELNGVNRIEDFIQQAELRGWLVNRLQVEAQVDLFNSLNEEIEFE(SEQ ID NO : 1121)>orf03442MFVADIMISDYSSAPIDFLLLNRVVFLYLPDFKEYQSDKNPFFEVFKVSKTKGIALDPFDEIIGRFQFG VRIV (SEQ ID NO 1122)>orf03450MGFSMKLIHDLNTHTTHSTAKMLYNVKAIKNDFSIRE (SEQ ID NO : 1124)>orf03453MEQLHFITKLLDIKDTNTQIIDVVNRDSHKEIIAKLDYDAPSCPECGSQMKKYDFQKPSKIPYLETTG MPTRILLRKRRFKCYHCSKMMVAETPLVKKNHQIPRIINQKIAQKLIEKISMTDIAHQLSISTSTVIRKLNDFHFE CNFRNLPKIMSWDVETVRGVTVSIGRWR(SEQ ID NO : 1125)>orf03462LDPWDGNSQKPRFQGLWKFIQRDSRKWRERRFYGPTFGKHLTNKKVFDKVFELFTRPGNIIIIFINFC GFTSEIRNRGKFFGLIEDNLKQVHPIFQTVFKTFLKDKEKIINALQLHYSNAKPEATNNLIKLIKRNAFGFRNFEN FKKRIFIALNIKKERTKFVLSRA(SEQ ID NO : 1126)>orf03466MVLYFWKVFQRVPNKLWKNMGENFQVRSLQDKIIQNLTNKGFSYFDAKMPIDEWDSQVDEETTQELISR DLISNILSMPESMKDTN (SEQ ID NO 1127)>orf03469MSKSHSFSISLGISNSFWNNIHTSECWYFLAEGKSNRSNSTISVNQMVFFINIQRFYCFAIEDFCLLRI (SEQ ID NO 1128)>orf03470LNTLLPPDNLCLFTIYLTGFSCICINSYCHNFWEIFNQLFYQLS(SEQ ID NO : 1129)>orf03475MKLLSIAISSYNAAAYLHYCVESLVIGGEQVGILIINDGSQDQTQEIAECLASKYPNIVRAIYQENKCH GGAVNRGLAEASGRYFKVVDSDDWVDPRAYLKILETLQELESKGQEVDVFVTNFVYEKEGQSRKKSMSYDSVLPVRQ IFGffDQVGNFSKGQYTMMHSLIYRTDLLRASQF(SEQ ID NO : 1130)>orf03476MYYLPVDFYRYLIGREDQSVNEQVMIKCIDQQLKVNRLLIDQLDLSQVSHPKMREYLLNHIEITTVISS TLLNRSGTAEHLAKKRQLWTYIQQKNPEVFQAIRKTMLSRLTKHSVLPDRKLSNVVYQITKSVYGFN (SEQ ID NO 1131)[2696]>orf03484MKRIQLNMNETKKYLVIKAIAQGKKTKKRACVELNLSERQINRLLLAYQQKGKEAFRHGHGNRNRKPKH AIPDEIKERVLKKYLSYETYKPNVLHFCELLAEEEGIKLSDTTVRKILYKKNILSPKSHRKTKKRVRKQAKLNLNQP LDNPILPTAKDFLEDPKKVHPSRPRKKFAGELIQMDASPHAWFGPETTNLHLAIDDASGNILGAYFDKQETLNAYYHVLEQILANHGIPLQMKTDKRTVFTYQALQL (SEQ ID NO : 1132)在一些實(shí)施方式中,優(yōu)選的INV200抗原選自以下多肽或其免疫原性片段 orf00159(SEQID NO :626)、orf00162 (SEQ ID NO :628)、orf00163 (SEQ ID NO :629)、 orf00164(SEQ IDNO :630)、orf00165 (SEQ ID NO :631)、orf00166 (SEQ ID NO :632)、 orf00201 (SEQ ID NO :639)、orf00209 (SEQ ID NO :645)、orf01109 (SEQ ID N0:747)、 orf01137(SEQ ID NO :751)、orf01138 (SEQ ID NO :752)、orf01309 (SEQ ID NO :783)、 orf01313(SEQ ID NO :786)、orf01315 (SEQ ID NO :787)、orf01431 (SEQ ID NO :810)、 orf01433(SEQ ID NO :812)、orf01434 (SEQ ID NO :813)、orf01537 (SEQ ID NO :824)、 orf01588(SEQ ID NO :831)、orf01642 (SEQ ID NO :842)、orf01656 (SEQ ID NO :847)、 orf01800(SEQ ID NO 875), orf01801(SEQ ID NO 876), orf01810(SEQ ID NO :879)、 orf01812(SEQ ID NO :880)、orf01818 (SEQ ID NO :882)、orf01988 (SEQ ID NO :913)、 orf01989(SEQ ID NO :914)、orf02105 (SEQ ID NO :925)、orf02106 (SEQ ID NO :926)、 orf02263(SEQ ID NO :947)、orf02264 (SEQ ID NO :948)、orf02459 (SEQ ID NO :968)、 orf02538(SEQ ID NO :987)、orf02539 (SEQ ID NO :988)、orf02541 (SEQ ID NO :990)、 orf02545 (SEQ ID NO :992)、orf02604 (SEQ ID NO :1003)、orf02608 (SEQ ID NO: 1007)、 orf02609 (SEQ ID NO : 1008)、orf02850 (SEQ ID NO : 1036)、orf03197 (SEQ ID NO: 1082)、 orf03439(SEQ ID NO:1120)、orf03448(SEQ ID NO: 1123)。7由23F鑒定的序列>orf00010LPVTFDFLIEGSTKGNIDKLDTATDCHNWFILTKRFLQECQFKFVTDQIVIIAFDGLFLSIKLRMNILA SCQNEFVNHFHIITYN (SEQ ID NO 1133)>orf00017MSLITHKRFISCNENIKHYKRLIDKAKKCVNDLMAEFNSVITTVTGIENRLGAVILAEIRNIHAFDNPA QLQAFAGLDSSIYQSGQIDLAGRMVKRGSPHLR (SEQ ID NO : 1134)>orf00027MQQYVDIKKQYPDAFLLFRMGDFYELFYEDAVNAAQILEISLTSRNKNADNPIPMAGVPYHSAQQYIDV LIEQGYKVAIAEQMEDPKQAVGVVKREVVQVITPGTVVDSSKPDSQNNFLVSIDREGNQFGLAYMDLVTGDFYVTGL LDFTLVCGEIRNLKAREVVLGYDLSEEEEQILSRQMNLVLSYEKESFEDLHLLDLRLATVEQTASSKLLQYVHRTQM RELNHLKPVIRYEIKDFLQMDYATKASLDLVENARSGKKQGSLFWLLDETKTAMGMRLLRSWIHRPLIDKERIVQRQ EVVQVFLDHFFERSDLTDSLKGVYDIERLASRVSFGKTNPKDLLQLATTLSSVPRIRAILEGMEQPTLAYLIAQLDA IPELESLISAAIAPEAPHVITDGGIIRTGFDETLDKYRCVLREGTSWIAEIEAKERENSGISTLKIDYNKKDGYYFH VTNSQLGNVPAHFFRKATLKNSERFGTEELARIEGDMLEAREKSANLEYEIFMRIREEVGKYIQRLQALAQGIATVD VLQSLAVVAETQHLIRPEF⑶DSQIDIRKGRHAVVEKVMGAQTYIPNTIQMAEDTSIQLVTGP匪SGKSTYMRQLAM TAVMAQLGSYVPAESAHLPIFDAIFTRIGAADDLVSGQSTFMVEMMEANNAISHATKNSLILFDELGRGTATYDGMA LAQSIIEYIHEHIGAKTLFATHYHELTSLESSLQHLVNVHVATLEQDGQVTFLHKIEPGPADKSYGIHVAKIAGLPADLLARADKILTQLENQGTESPPPMRQTSAVTEQISLFDRAEEHPILAELAKLDVYNMTPMQVMNVLVELKQKL(SEQ ID NO 1135)>orf00033MRRKYKSIALKKELANDSGKKKFHAMKAQAIVTSQGRIVSIAMI(SEQ ID NO : 1136)>orf00042 LTNLSSVDSEELFQFYRERGNAENFIKERKAGFFGDKTDSSTMIKNEVRMMMGCLAYNLYLFLKQLAGD EVKALTIKRFRRLFLHIAGKYVSTARRHILKFSSLYAYSKQFQALFDTICQINLILPVPYRARGQGKTA (SEQ ID NO 1137)>orf00051LFDDRQAINICPPTNGSLRLTSLQVDQNPCPPSTNLNKILARSQFLNHIQQISLSLELLQANLWNLV (SEQ ID NO 1138)>orf00055LSVHFCSSHRCLLVRYNDTYSTKKGLKFETFLSVFRYDFLGM(SEQ ID NO : 1139)>orf00086VDRTDEVSSKHGFEVVDETDEVSSKHGFEVADRTDEVSSKHGFEVADRTDEVSSKHGFEVADRTDEVS SKHGFEVADRTDEVSSKHGFEVADRTDEVSSKHGFEVADRTDEVSSKHGFEVADRTDEVSSKHGFEVADRTDEVSS KHGFEVADRTDEVSNIYTAR(SEQ ID NO : 1140)>orf00088MDFFNYLLWMICHNHGLHTLLLSKDCVCHTARDKDGNHRIKSVFPTKGQTCYQHDSSIYQERNTTDILT RFLANSQADDIRPTTGDIVSKSKTNPQTHNNTPKKGIDNGILRQGCHRDKLDKEGTHRYRDKGKDGELMANLIPS (SEQ ID NO 1141)>orf00096MKIKEQTRKLAAGCSKHCFEVVDETDKVSSKHGFEVVDETDEVSSKHGFEVVDETDEVSNHTYGKATLT WFEEIFEEY (SEQ ID NO : 1142)>orf00103LQNDKNHKLFDNYTCQKEKDVLRCKQVKRKEERSYDVGTRIYTIYDFLLF(SEQ ID NO : 1143)>orf00105MKIKEQTRKLAAGCSKHCFEVMDRTDEVSSKHGFEVVDETDEVSNHTYGEVKLTWFEEIFEEY (SEQ ID NO 1144)>orf00106LFFKDEKQALYTKPKTKSSSFRASKVSNQTIVATTRTDCQVIALNLCDKLENGVVVVVQTTHHIGIDD VIYSKIFQHLTHSIKMSLAFFIKKVQDRRRILYCHLVFFFLRVQDTKRIFLQATLAILRQGLLERCQIVNQGLAVG CTALRISKSVEVQFDTLNTDFLQKMGCHSDCFHIGSWIARAKTLNTNLVELAQAPCLWTLITEHRSHVVELAWLL HFWGEEFIFHIGTDNGRSSFWTEGNMAVTLVIEIVHFLGYDIGRISDRAADNLVMLKNGRAHFCVVVALENFTGK ALNVLPFGRFSR (SEQ ID NO : 1145)>orf00114MEQIGKVFRQLRESRNISLRQATGGQFSPSMLSRFETGQSELSVEKFLFALENISASVEEILFLARGFQ YDTDSELRKEITDVLEPKNVAPLEDLYRREYQKHAHSHNKQKHILNAIMIKSYMKSMDERVELTAEEGKVLHDYLFS TEIWGIYELNLFSVSSPFLSVSLFTRYVREMVRKSDFLMEMSGNRNLFYTILLNGFLASIECEEFTNAYYFKRVIEEHFYKENETYFRIVYLWAEGLLDSKQGRVKEGQKKMEDAVRIFEMLGCNKSAEYYRNTTEC(SEQ ID NO 1146)>orf00118MQEHYTPKGKHLTIDNRRLIERWKNENKSNREIAGLLGKAPQTIHTEVKRGTTLQQVRKGLYKKVYSA DYAQTVYQFNRKRSVKKLILTKEIREKILHYHKQKFSPEMMVNKKQVKVGISTIYYffFHNGHLGLTKADMLYPRKR KGVKKQASPNFKPAGKSIEERPDVINLRLENGHYEIDTVLLTKIKNYCLLVLTDRRSRHQIIRLIPNKTAESVNQ ALTLLLGEHHILSITADNGSEFKRLSEVFPEEHIYYAHAYSSWERGSNENHNRLIRRWLPKGTKKTTPKEVAFIE NWINNYPKKCLDYKSPSEFLLGG (SEQ ID NO : 1147)>orf00121MKIKGQTRKLAAGCSKHCFEVVDRTDEVSNHTYGKATLT (SEQ ID NO : 1148)>orf00124 VVPFSDTFKDRNQVDIFTIKISRCNSSTIGENSWDIHISNSNHRSRHVLVTATDSDEGIHVVTTHSRLD GVRDDVTRC (SEQ ID NO : 1149)>orf00139MDLKFEGVDLEYKKAKNNLPESFffETYSAFANTNGGKIILGIDEKNIDTYQRVNRLPAKL(SEQ ID NO 1150)>orf00156LSIQVETLELRVIFKEIKEIVKQFHQLHTMAFKRQVPLTVPVTM (SEQ ID NO 1151)>orf00171VQKLKKAIYKAHLKDSDDFRPETSTPNLFESCLKLCPCFLSS (SEQ ID NO : 1152)>orf00172MGALGYYEGFVPYVSNQYKNQAEEEGKPLSDKYIFEKILGKTYAAFKKDQINERVEKLGKLKPITINYN GKSEVIDSKEKLQELMNKAVKDEVAQI (SEQ ID NO: 1153)>orf00173MMGDGMKEFQFERKQRFSLRKYAIGACSVLLGTSLFFAGMGDQPVQDTETSSALISSHYLDEQDLSEKL KSELQffFELENKLLNLffEH (SEQ ID NO: 1154)>orf00177VNIAKTSIIKAHTTKEDGIDHTFTRFNIMSIFYSTRKIFLDKLNSTNRQFLGYIISTRCYQSFNSVSQS IHTSSSSQAFRFGKHEFRVINRDKSKAILVNHYHLNLAFFISNHIVNGNFC(SEQ ID NO 1155)>orf00178MKPFIILWSSTICSHDRNTTSCILWRTPAKTDDKVTAMFLQSSYPICDIFTSRVWLYIAKDDIFDSFCI QffF (SEQ ID NO : 1156)>orf00194MHIPFARWQAFSLYNISINIHHYNIGFFDFKEINTRRGNCHQLFFTIENTEIPTCSFRQICFY (SEQ ID NO 1157)>orf00205MNIAIRIILNFFRVMGNHQNSLAMMMGAVVHEFVKFIFTSCIHPRCRLV(SEQ ID NO : 1158)>orf00206MLLIMSIQTTEPAFSRIATRLDKFIDRTWKTSIKTGNLLRKIGYSQFLTLRICL(SEQ ID NO: 1159)[2754]>orf00207LQNSKTSLDERRLSRSIFPSQGNKFPTINTIIDMFKNRLLIIIEGQILYRNISHYLISPTKAVKNR (SEQ ID NO 1160)>orf00220MSNSFVKLLVSQLFANLADIFFRVTIIANIYIISKSVIATSLVPILIGISSFVASLLVPLVTKRLALNR VLSLSQFGKTILLAILVGMFTVMQSVAPLVTYLFVVAISILDGFAAPVSYAIVPRYATDLGKANSALSMTGEAVQLI GffGLGGLLFATIGLLPTTFIILVLYIISSFLMLFLPNAEVEVLESETNLEILLKGffKLVARNPRLRLFVSANLLEIF SNTIffVSSIILVFVTELLNKTESYWGYSNTAYSIGIIISGLIAFRLSEKFLAAKWESILFPLVAMAIVTLTILYFPN AQMFLLFSALVGMLSQLKEVPESVFLQETVEENHLVNVYSVLEVISTLAFSVFVLLMSYITESFGISISFffLSAICL MIEAILIYIRRDYFK (SEQ ID NO 1161)>orf00221MSLVHNIIEDOTTESLIRKYLHSGVIINGQRYKTLVGTPQGGNLSPLLSNIMLNELDKELEKRGLRFVR Y ADDCVITVGSEAASKRVMYSVSRFIEKRLGLKV匪TKTKITRPRELKYLGFGFWKSSDGWKSRPHQDSVRRFKLKL KKLTHRKffSIDLTRRIEQLNLSIRGffISYFSLGNMKV (SEQ ID NO : 1162)>orf00222MSKLLDKILSRE匪LEAYNQVKSNKGSAGIDGMTIEEMDNYLRQNWRLTKELIKQRKYKPQPVLKVEIP KPDGGIRQLGIPTVMDRMIQQAIVQVMSPICEPHFSDTSYGFRPNRSCEKAIMKLLEYLNDGYEWIVD (SEQ ID NO 1163)>orf00229LHFNQTSLKTASCRLQGYTSSCDSSTDNQEVQGAFLHFFN (SEQ ID NO : 1164)>orf00247MFCLTFICLIRRSGYLGSYLLLCRMNHTSHKKTGNSYTSYSNTKFTN(SEQ ID NO : 1165)>orf00248LPSEIKAKLDAAFEQFKKDTLPTEPGKKVAEAEKKVEEAKKKAEDQKEKDLRNYPTNTYKTLELDIAE SDVEVKKAELELVKEEAKESRDEKKINQAKAKVENKKAEATRLKNIKTDREKAEEAKRRADAKLQEANVATSEQDK SKRRAKREVLGELATPDKKENDAKSSDSSVGEETLTSPSLKPEKKVAEAEKKVEEAKKKAEDQKEEDRRNYPTNT YKTLELEIAESDVEVKKAELELVKEEAKESRDEKKINQAKAKVENKKAEATRLKNIKTDREKAEEAKRRADAKLQ EANVATSEQDKSKRRAKREVLGELATPDKKENDAKSSDSSVGEETLTSPSLKPEKKVAEAEKKVEEAKKKAEDQK EEDRRNYPTNTYKTLELEIAESDVEVKKAELELVKEEAKESRNEEKIKQVKAKVESKKAEATRLENIKTDRKKAE EEEAKRRAAEEDKVKEKPAEQPQPAPAPQPEKPTEEPENPAPAPAPKPENPAEKPKAEKPADQQAEEDYARRSEE EYNRLTQQQPPKAEKPAQPSTPKTGWKQENGMWYFYNTDGSMATGffLQNNGSffYYLNSNGAMATGffLQNNGSffYY LNANGSMATGWLQNNGSWYYLNANGSMATGWLQYNGSWYYLNAN⑶MATGWLQNNGSWYYLNANGDMATGWLQNN GSWYYLNAN⑶MATGWLQYNGSWYYLNAN⑶METGWVKD⑶TWYYLEASGAMKASQWFKVSDKWYYVNGSGALAV NTTVDGYGVNANGEffVN(SEQ ID NO: 1166)>orf00254MDREILKFFQDLLSILSHNDMITLFCQKCCNSFSNHFLVICN (SEQ ID NO : 1167)>orf00261MTRKLNPSYTNVASATTLTFNQVASTFRKACLDHVVNLTRNNLKGICQLTPLQLHDTRLI(SEQ ID NO 1168)[2772]>orf00300LVSVFYSLLQVDNVDSVTFSKDVLSHLRIPATSLVTKVYTSLKKLFH(SEQ ID NO : 1169)>orf00309 [2775]LIVWILKNHTDLTTYIPNIFLSQTLAINYNLSGFCFQ (SEQ ID NO 1170)>orf00310MPYNRKPFSTFHVKRNILHIVVVLIFFIAKRKIFYINY (SEQ ID NO : 1171)>orf00314MFKKMSNSSRILFYISVNFCDKRIYRTKLYSDTPVNLFKFLFRQKSNCQSVGQTSSINLFFYSWIVFFF KNNLCHSIPSIK (SEQ ID NO : 1172)>orf00327LADGSRKLAEGGTKLTSGLEDLQTGLASLGQGLGNASDQLKSVSTESKNAEILSNPLNLSKTDNDQVPV NGIAIAPYMISVALFLQQYQQI (SEQ ID NO: 1173)>orf00356MEMSFIAQDFDKLNIITVLESRTQAIIRNPMNTRLSSATGSSFNKIVRN(SEQ ID NO : 1174)>orf00358MELAETSIVKKNHQIPCIINQKIAQKLIEKTSMTDIDHQLSISTSTVIRKINNFHFEHDFSRLPEIMS (SEQ ID NO 1175)>orf00364MNYIDTNEMLFVETPRKVITSDELRKKNTKYLDQKEFKLFIQNLKDEALCDYRITKYIRIAKVLFLTGM RYGELAALNYKEDIDFSKKTIHIKHTYDFRQKERTTPKTIKSDRVITAPQKVLDIIKEQIIENATNGFDTDFIFINT LGEPITNARVICALKRHGQKIGIEKNITTHTFRHSHISLLAELGIPLTAIMDRVGHSDSKTTLEIYSHVTQKMVSDI SSKLDKIKF(SEQ ID NO: 1176)>orf00365MWMEELPNGKYKFFERYKDPYTEKLKKVSVTMEKKTPQARNQAAILLQEKIKQKLGEKQHSVSNITFEK LYEEFEENWKHGVKNSTVYASKNVKKEILKQIEGDYLVRNLIDVYYKK(SEQ ID NO: 1177)>orf00367MEIDKVKADLKQVGKRVADLSQSITNEEQTKNAFIMPFFQALGYDIFNPLEFVPEFTADVGIKKGEKVD YAIILDGEPQILIECKSITENLTKHDSQLFRYFVTTKSKFGILTNGREYKFFTDLDEPNKMDTTPFLTIDVTDIKEN QFTEIIKFHKENFDIDNIVSSASELKYLNNLKAFLTENITTPSDSFLRYLTSEIYEGRVTQNILTTFSPIIVKGFNQ FITERVNEKLSAALNTSVETKVTTDIPKVEAEAEEIVEVTDEIITTPAELEVYTVVKMLARDVVSPERVFYRDNRSY FNVLVDDNIKKWVLRYRSNSKKSTIEIRDKGIFPVSTPLEVANYANEILEVIKKFS(SEQ ID NO 1178)>orf00368MTLAKLCEEYQVELCLFDGSNWHNSGFYNPDTNVLAIDHNLTPEQQIQVALHELGHKDHTRSEHQNARL RCENEADRNMIHHLVKDALENLDDPTEFDYLKFMSYYNLKTMTNEIMVKEEYLALVN (SEQ ID NO: 1179)>orf00369MYRLDIDKKALKQLKKLDTPTRKQILSWLAKNIENTTNPRQHGKALKANLAGYWRYRVENYRIICDIQD DKLVVLAVEIAHRRDVYK (SEQ ID NO: 1180)>orf00370MTITINFTEKNSYITDYLNKHGIDTTTMDFDDFMALMEDIEDARAADQAYMEYLADPATYTMDEVLDELGLTREDIA (SEQ ID NO 1181)>orf00371 MFETFEKIKELAKKRGKALGQVEEDLGYGRNTLYKIKNSTPNAERIAEIANYFNVSTDYLLGRTDNPAI AGSDEFAQVNGQIIDLRKAAANTMLFDGKPLNEDDIDFITSVLSAHFKSKGER (SEQ ID NO: 1182)>orf00372MVSILKNLEQEKDHLEKVIKVVSAGGKFLRLPYQKSHARLVRI (SEQ ID NO : 1183)>orf00373MPDIANGRERVIAFLKEKGIKKATLAVAYGFKRQEVTNILSGTTKGPRANSFILQVIEDYGIE(SEQ ID NO 1184)>orf00374MRPKRYPYSGQKESTFVKADPELVEKLLRNTSFLECLQKKPINFQIDSEEFKRLSYEAIHDTSQVTQ (SEQ ID NO 1185)>orf00377LKNREEEffQGIIAKNAILLIIAPFYFLIIVKNGVLSKIKTVTEITAYQL(SEQ ID NO : 1186)>orf00378MREVIQELLDSSMSTSAISQGAGVPWTTVSDLRKGKTSMDKMALLTAEKLYEFATTDKQ(SEQ ID NO 1187)>orf00382 VEEVEVAEVKNARVSLTGEKTKPMKLAEVTSINVNRTKTEMEEFNRVLGGGVVPGSLVLIGGDPGIGKS TLLLQVSTQLSQVGTVLYVSGEESAQQIKLRAERLGDIDSEFYLYAETNMQSVRAEVERIQPDFLIIDSIQTIMSPE ISGVQGSVSQVREVTAELMQLAKTNNIAIFIVGHVTKEGTLAGPRMLEHMVDTVLYFEGERHHTFRILRAVKNRFGS TNEIGIFEMQSGGLVEVLNPSQVFLEERLDGATGSSIVVTMEGTRPILAEVQALVTPTMFGNAKRTTTGLDFNRASL IMAVLEKRAGLLLQNQDAYLKSAGGVKLDEPAIDLAVAVAIASSYKDKPTNPQECFVGELGLTGEIRRVNRIEQRIN EAAKLGFTKIYVPQNSLTGITLPKEIQVIGVTTIQEVLKKVFA(SEQ ID NO: 1188)>orf00389VNIATLQNGHILGWQIQHIANKLTSNFWIAKDFLSYQVIGffANARMTYSHISSLFIISQF(SEQ ID NO 1189)>orf00391VSITFSLTNFFKILINLTAQVSPQVIDEKILMMDLNLNNYLSTVIQLRQDVYTGIKILHRVRHGE (SEQ ID NO 1190)>orf00392MSRYSYSLDSRKIVFEISCFKEKKASLTLFFHLFESSIMKLATQPSFSSFYSELK(SEQ ID NO: 1191)>orf00396MKIKEQTRKLAAGCSKHCFEVVDRTDEVSSKHRFEVADRTDEVSSKHRFEVADRTDEVSNIYLRQGDVD VV (SEQ ID NO : 1192)>orf00408LSLLDLRGSLCLRIYLHEPLITTVSQDFTSLSDISHF (SEQ ID NO : 1193)>orf00411[2823]MDFKSFIIGLVVGIFGPYMDDLIRKKFLKSSEKKTEKSVKK (SEQ ID NO 1194)>orf00434 MFEKIKGINIKSGIFEDETKLELFEGNFEGTNPVQNDRASLLFGRNGSGKSTIARGINQLKNGEIGTDR VSFIDKNNNNIVLSDTERKSIFVFNEHYVDQKVKIAQEGLDTIVILGEQVDIDEELDRLRTQLSESQIESQDYYAEY EEYLDEKNEKSPDFWKKEMTDSLKGVGNWAERDREIKGNRAASPVHNNTFQNFVDLQPILDKNELEVEFNNKKARYF SIRDSAVTINNELSLPDINFDSNELSTLLSEKIEEPELNSRDKYLLTLLSDSTKGERHLREVKDFFEDEHQKKCPFC TQSVSEDVKVELTNGITKLLSRAVEEHQSALRGKKIDEINQDFSGYEQIDPILIQSYQNSINALNAKFNEINSIIDK KIDNPYNIVELPNISFSQELSQAEHDIEKINQAIIKHNSEISGIQKLKVDLLQINNELAFYEIQDAYKKFQEKTNKK AICENNYNNSSKRVKDYEKQISDLEDKKLNIDIAVDEINKSLNYIFFSKNRLAIQNQNGKYYLLSRGKSVVPSRVSV GERNALALCYFFTEIIQQRELADAYSHEYFIVIDDPISSFDMENKVGITSYLKYCLTRFFKGNSNTRVLLMTHDKQT IYDFDIFLKEIMESCKEEEGGQKSKYKKLELVSGKLQEFKTSTHDYTELLEIVFGYALGNSTPTSESFVGNAMRKIL EAYGSFNYKKGIAELTTDPLIVEKIDKEYRTYFENLMYRLVLNGESHFKDPVKTLSIDFFDTISDEERKKTARDLLV LLYLLDDLHVLKHLEGVSNAENRLEQffKCEILE (SEQ ID NO : 1195)>orf00458MIE⑶RDCADIVTQLTAVKSSVERVIEMIITENLTECINQPLDDSEAQKERLEKAIRYLIKRK(SEQ ID NO 1196)>orf00460METSISMADFYGKYQNENLELIDVREAHEFQAGHAPGAKNLPLSTLEQGYKELKPDHEYYVICQGGVRS ASTCQFLSSQGLTVTNVEGGMNAWPGQVE (SEQ ID NO: 1197)>orf00462LGGKSCLLEDRLCDIAAQTTVAADDVGLFFVQFISFLLDTLSVFDTIVQN(SEQ ID NO : 1198)>orf00466MKIKDQTRKLAAGCSKHCFEVVDRTDEVSSKHCFEVADRTDEVSNIYTARRR(SEQ ID NO : 1199)>orf00467MKLLSIAISSYNAAAYLHYCVESLVIGGEQVGILIINDGSQDQTQEIAECLASKYPNIVRAIYQENKGH GGAVNRGLAEASGRYFKVVDSDDWVDPRAYLKILETLQEFESKGQEVDVFVTNFVYEKEGQSCKKSMSYDSVLPVRQ IFGffDQVGNFSKGQYIMMHSLIYRTDLLRASQF(SEQ ID NO : 1200)>orf00468MYYLPVDFYRYLIGREDQSVNEQVMIKCIDQQLKVNRLLVDQLDLSQVSHPKMREYLLNHIEITTVISS TLLNRSGTAEHLAKKRQLWTYIQQKNPEVFQAIRKTMLSRLTKHSVLPDRKLSNVVYQITKSVYGFN (SEQ ID NO 1201)>orf00476MSLQIKLKKLAKELSKLLKDSNLETVDKDVLENSQKELQKAVLFLADEKGSEHTEAEVIDNLKEVIAKL KANA (SEQ ID NO : 1202)>orf00483MKIKEQTRKLAAGCSKHCFEVVDKTDEVSYIYLRQGEADAV (SEQ ID NO : 1203)>orf00503MKIKEQTRKLAAGSSKHCFKWDGTDEVSSKHCFKWDGTDEVSSKHCFEWDRTDEVSNHIRQ ⑶ VDV V (SEQ ID NO : 1204)[2844]>orf00509MNDDDSRCIHIERDGKTIEFGYLNISSTDRNTSHADGLVGIFNSNFSGVRVRGIAVFLNGPDNLDTTLV GNFQTIffNFRIICIHS (SEQ ID NO 1205)>orf00510LEFNFCRSIIKNGRDNLPNTNSTSGMATRWANHNWSDDIKDRLKTK (SEQ ID NO : 1206)>orf00515MSNVDKIRKIHIIVCWMYIFLSFRAIINDTEYFLLIFLAFIYSIVSLPLYSVKNKIVSICLVINSILLM SFPILINKFFPESFLTYIVLISVFITELIIFHLIGKDFDTKLTNEYKKISQFRSKVSQSPWIKYLEISSFILTIFPS ILYGTVDNHVLTLIFLIKICVDTTIKFLFIRLFDTSTLMKRRIFFLFALDVIAYLFLGYLLVIQKAGYLFSVLLLFS NFSVPFI KEKEYELFKNSK (SEQ ID NO : 1207) [2850]>orf00516MNKKKMILTSLASVAILGAGFVASSPTVVRAEDAPQVVEKSSLEKKYEEAKTKADTAKKDYETAKKKAE DAQKKYDEDQKKTEEKAKKEKEAAKKVDDASLAVQKAYVEYRKVQESRSNYRNRSDYNKKLAEAQVKIDEANKKLTA ANNEFKTVRAVVVPEPNALAETKKKAEEAKAEK(SEQ ID NO : 1208)>orf00518LEQEVATAQHQVDNLKKLLAGVDPDDTEAIEAKLKKGEAELNAKQAELAKKQTGLEKLLDSLDPEGKTQ DELDKEAAEAELNKKVESLQNKVADLEKEISNLEILLGGADSEDDTAALQNKLAAKKAELAKKQTELEKLLDSLDPE GKTQDELDKEAAEAELDKKADELQNKVADLEKEISNLEILLGGADPEDDTAALQNKLATTKAELEKTQKELDAALNE LGPDGDEEETPAPAPQPEQPAPAPAPKPEQPAPAPKPEKSADQQAEEDYARRSEEEYNRLTQQQPPKAEKPAPAPAP KPEQPAPAPKTGWKQENGMWYFYNTDGSMATGffLQNNGSffYYLNSNGAMATGffAKVNGSffYYLNANGSMATGffVKDG DTWYYLEASGAMKASQffFKVSDKWYYVNSNGAMATGffLQYNGSffYYLNANGAMATGffAKVNGSffYYLNANGSMATGff VKDGDTWYYLEASGAMKASQWFKVSDKWYYVNGLGALAVNTTVDGYEVNANGEffV (SEQ ID NO : 1209)>orf00519LTISFKKQFLSSSLSSLTKRVIMNTAQATFNREAHTTFNRE (SEQ ID NO : 1210)>orf00525MKIKEQTRKLAVGCSKHCFEVVDRTDEVSSKHRFEVVDRTDEVSNIYTARRS(SEQ ID NO : 1211)>orf00539LKKRMNRffQFLLNQSKEMVGILLLKMKEQELIEFVVNL (SEQ ID NO : 1212)>orf00540LIKVIKRKAFGFRNFNNFKKRILMTLNIKKESTNFVLSRL (SEQ ID NO : 1213)>orf00544MTYNEKRLTNSLERVHMEQLKNTTDLLGLKDKNIKILSVLKYQTHLVVQAKLDSPAPPCPHCQGKMIK YDFQKASKIPLLDCQGLPTVLHLKKRRFQCKNCLKVVVSQTSIVKKNCQISNMVRQKIAQLLLEKQSMTEIAHRLA VSTSTVIRKLREFKFETDWTKLPKVMSWDEYSFKKSKMSFIAQDFESKSILAILDGRTHAVIRNHFQRYQREVRE LVEVITMDMYSPYYRLAKQLFPKAKIVLDRFHIVQHLSRAMNRVRIQIMNQFDRKSLEYRALKRFWNPRFFVSRL GLNQSTGLIYYTRIASSSVRNDSISPRFECT (SEQ ID NO 1214)>orf00545MGYSLKKSCTYCEQDPEKVNRFLKELNHLSYLTPIYIYETGVETYFYLEYDRALSRQLVSLEEDIII (SEQ ID NO 1215)[2866]>orf00552[2867]MNIAVIGLGHVGLAYALLFASKYKVVAYDIDSVKINNLKKGILPSKNEELMKFFCENNLNITFFDTFSE IKNNIDYYIIALPTDYDEKIGSFNTYEIEQTVSKILRVKPNGKIILKSTVPFGFSNKLKRLFDTKNIIFVPEFLREG CSIYDNLYPSRIVVGDETVEGRKIAELFLSISTHSTANIKNVMLVSPTEAEAIKLFSNTFLALRVAFFNELDSFAER RSLNAEVVIKGVCLDPRIGNFYNNLSFGFGGYCLPKDTKQLKKEFIEINAPVIEAIDISNTNRKQFIVKQILERKPK IVGIYKLGMKYNSDNYKESAILSIINELLIVGIKILVYEPNLNVSIDNVIFEKNFELFTKQSDLIVANRWDRGLEAY KDKVYTRGIffIRD (SEQ ID NO 1216)>orf00554MLNLQFAETMELTEAELEIVYGGEFGNNAVIPAGAffGGFGTPffSITNFffKKNFNDRPDFDSDRRRY (SEQ ID NO 1217)>orf00599MGLDVGSKTVGVAISDPLGFTAQGLEIIQINEEQGQFGFDRVKELVDTYKVERFWGLPK 匪 NNTSGPR VEASQAYGAKLEEFFGLPVDYQDERLTTVAAERMLIEQADISRNKRKKVIDKLAAQLILQNYLDRKF (SEQ ID NO 1218)>orf00635LNPSYSFGKKDQFALEHCFCIKLSIFARAVTLFVSCIN (SEQ ID NO : 1219)>orf00656MITGTAFILIMSLSARKLPYTIRSSVASLQQIAPSIEEAAESLGSSRLNIFAKITTPMMLSDIISGAIL SffVTLISELSTSILLYNVKTRTMTVAIYTEVLRGNYGVAAALSTILTVLTVGSLLLFMKISKSNSITL (SEQ ID NO 1220)>orf00657MLIGEGYRTFPVLIYTQFISEVGGNSAFAIMAIIIALAIFLIQKHIANRYSFSMNLLHPIEPKKTTKGK MAAIYATVYGIIFISVLPQIYLIYTSFLKTSGMVFVKGYSPNSYKLAFNRMGSAIFNTIRIPLIALVLVVLFTTFIS YLAVRKRNLFTNLIDSLSMVPYIVPGTVLGIAFISLVYLEVDFL (SEQ ID NO : 1221)>orf00658MECKKLNIWTASSFFLFLTYLVFLVYPIVTVLKQALIHEGQFSLANFVTFFSKAYYSETLVNSFRVSITATVTSLVVGTLLAYLFSMYDFKGKKFLQILIIIASMSAPFVGAYSWILLLGRNEVITKF LTNALYLPAIDIYGFKGIVLVFTLQLFPLVFLYVAGTMNSIDNSLLEAAE SMGSFGFKPIVTVVLPLLVPTLLAAP CLYL (SEQ ID NO : 1222)>orf00660LLSTTEFIGLSIRILSNLHEFKILVGLLNQFFFWNLLLHKTKSNVVSDSQMWENSVVLENQPDIAFAGF HIIDFCIIEVKFSIFDTVETCNHTKKGRFPTS (SEQ ID NO : 1223)>orf00679MITIKKQEIVKLEDVLHLYQAVGWTNYTHQPEMLEQALSHSLVIYLALDGDAWGLIRLV⑶GFSSVLV QDLIVLPIYQRQGIGSALMKEALEDYKDAYQVQLVTEETERTLGFYRSMGFEILSTYNCIGMTWMNRKK (SEQ ID NO 1224)>orf00710VLKIRYHKQFKKDFKLAMKRGLNAELLEEVLKIffFKKKNFLLDIVIIN(SEQ ID NO : 1225)>orf00714[2888]MLGSMFVGLLVGFLAGTLTNRGEHMGCFGKMFLGWIGAFIGHLLFGTWGPIIAGTAIIPAVLGSMIVLA IFffRRGS (SEQ ID NO 1226)>orf00741MIDDIPKRVNDVIGQAGNNAKTSRPHVGIGKSHISVPFLFPYHTANRIKNQEKVIF(SEQ ID NO: 1227)>orf00755VAIDKIAGITSEKDSRAHQIFRISPTCSRCFCNDELVKWVARTIFLQLTKRCCLRSGNITRSNSVTLDI GSTVFRRNVAGQHFQAPFSSSISANCFTSQFAHHRTNIDNLSMPFLYHRRNNCL (SEQ ID NO: 1228)>orf00756 LFDLLDHGLDTVLVCHVTDISMGFDANFTISFNPFIDQILIDIVKDNSSAGFSVGFGNSKSNSIRSAGD ESNFSF (SEQ ID NO : 1229)>orf00768MKSLARLLIIHVFISIFLFFALISGAVSHTVLLLLLLFLPALNKGLEKIQSKRIPVLNAALFFLLISFP QLLTNPVQWKFSIFLVVTIISSLAYFYNFYQVVKEVDQKQLI(SEQ ID NO: 1230)>orf00769LEAASEIETEFQSWIVLVVFNHIDGLSRDTDILGELELGNAQFLAKFFHTIHLVSFLICVVYI (SEQ ID NO 1231)>orf00774MKWTKRVIRYATKNRKSPAENRRRVGKSLSLLSVFVFAIFLVNFAVIIGTGTRFGTDLAKEAKKVHQTTRTVPAKRGTIYDRNGVPIAEDATSYNVYAVIDENYKSATGKILYVEKTQFNKVAEVFHKY LDMEESYVREQLSQPNLKQVSFGSKGNGITYANMMSIKKELETAEVKGIDFTTSPNRSYPNGQFASSFIGLAQLHEN EDGSKSLLGTSGMESSLNSILAGTDGIITYEKDRVGNIVPGTELVSQQTVDGKDVYTTLSSPLQSFMETQMDAFLEK VKGKYMTATLVSAKTGEILATTQRPTFNADTKEGITEDFVffRDILYQSNYEPGSAMKVMTLASSIDNNTFPSGEYFN SSEFKIADATTRDWDVNDGLTTGGMMTFLQGFAHSSNVGMSLLEQKMGDATWLDYLKRFKFFGVPTRFGLTDEYAGQ LPADNIVSIAQSSFGQGISVTQTQMLRAFTAIANDGVMLEPKFISAIYDTNNQSVRKSQKEIVGNPVSKEAASTTRN HMILVGTDPLYGTMYNHYTGKPIITVPGQNVAVKSGTAQIADEKNGGYLVGSTNYIFSVVTMNPAENPDFILYVTVQ QPEHYSGIQLGEFATPILERASAMKESLNLQSPAKNLDKVTTESSYAMPSIKDISPGELAEALRRNIVQPIVVGTGT KIKETSVEEGTNLAPNQQVLLLSDKVEEIPDMYGWKKETAETFAKWLDIELEFEGSGSVVQKQDVRTNTAIKNIKKI KLTLGD (SEQ ID NO : 1232)>orf00776MVDRTDEVSSKHGFEVVDKEKLMWFEEVFEECKKILVS (SEQ ID NO : 1233)>orf00783MEGVNHVDIIKVSCCSFISQVNWMMKGKIPNREGFKFSVARFDAIDLVVVHIGHTRCQFSRTGSRSGYD NQVATGFDVVVFAHAFWGNDVIHIRRISFDWIMKIRINSVFLKLVAEGICSGLASVLCNDNGTNKNP (SEQ ID NO 1234)>orf00784MFNVASINGNHNLNLLFQFLQELDFVVRFITRKDTSSVEIF (SEQ ID NO : 1235)>orf00790LTNQDLQAGTYLVKDYREIILSQDALEKVATNLKLDMPAKTLASKVQVAVPADTRIVSISVKDKQPEEASRIANSLREVAAEKIVAVTRVSDVTTLEEARPATTPSSPNVRRNSLFGFLGGAVVTVIAVLLIELLDTRVKRPED VEDVLKIPLLGLVPDFDKIK(SEQ ID NO : 1236) [2910] >orf00791 MPTLEISQAKLDSVKKAEEYYNALCTNLQLSGDGLKVFSITSVKIGEGKSTTSANIAWAFARAGYKTLL IDGDIRNSVMLGVFKARNKITGLTEFLSGTTDLSQGLCDTNIENLFVIQAGSVSPNPTALLQSKNFTTMLETLRKYF DYIIVDTAPVGVVIDAAIITRNCDASILVTEAGEINRRDIQKAKEQLEHTGKPFLGIVLNKFDTSVDKYGSYGNYGN YGKNKK(SEQ ID NO 1237)>orf00792MNEKILRSSLAIIQSFLVILLTYLLSAVRETEIVSTTAIALYILHYFVFYISDYGQDFFKRRYLIELV QTLKYILFFALAIGISNFFLEDRFSISRRGMIYFLTLHALLVYVLNLFIKWYWKRAYPNFKGSKKILLLTATSRVE KVLDRLIESNEVVGKLVAVSVLDKPDFQHDCLKVVAEGEIVNFATHEVVDEVFINLPGEKYNIGELVSQFETMGI DVIVNLNAFDRSLARNKQIREMAGLNVVTFSTTFYKTSHVIAKRIIDIVGALVGLILCGLVSIVLVPLIRKDGGS AIFAQTRIGKNGRQFTFYKFRSMCVDAEAKKRELMEQNTMQGGMFKVDDDPRITKIGCFIRKTSLDELPQFYNVL KGDMSLVGTRPPTVDEYEHYTPEQKRRLSFKPGITGLffQVSGRSEIKNFDEVVKLDVAYIDGffTIffKDIEILLKT VKVVFMRDGAK (SEQ ID NO: 1238)>orf00793MKKSVYIIGSKGIPAKYGGFETFVEKLTAFQQDKAIQYYVACMRENSAKSGTTEDVFEHNGAICYNVDV PNIGPARAIAYDIAAINRAIEIAKENKDEDPIFYILACRIGPFIHGIKKKIQEIGGTLLVNPDGHEWLRAKWSAPVR RYWKISEGLMVKHADLLVCDSKNIEKYIQEDYKQYQPKTTYIAYGTDTTRSVLKSSDEKVRSWFKEKNVSENEYYLV VGRFVPENNYESMIRGFLASNSKKDFVLITNVEQNKFYNQLLAKTGFDKDPRVKFVGTVYEQELLKYIRENAFAYFH GHEVGGTNPSLLEALASTKLNLLLDVGFNREVAEDGAIYWKKDNLHEIIETSEQKTQKEIDEKDILSIKQVTERFSW ELIVNEYEKLFLCEK (SEQ ID NO : 1239)>orf00794VTIKINNLFFVCLSFFGIVLSSSQVIVNLGLSSIIQYISYFMLMLCVFLTLIKNTLNVFANRIIYFLII SFLFIIGINLQNLPLSRKIYLSFSMLIISSLSTLPIKLINNLSDLRRISYYLLHSIFLSVFLGLVFKISLVTVAVEG IGFSYGFNGGLTHKNFYAITILVSYILLYVSRKYDAKHQIDSFVLWLDLFLLLISNTRTVYIILVVFffIIINRNFIN NIKKEHRLVVTATTIVISLLALTFFFKHIINNSESYSHRVLGVVNFFKYYESDRFHLFF⑶AELAFGNTTKGYGHNI RSVLGWDGTVEMPLLSVMIKNGYVGLVGYIIVLFKFISSIISVKNSTKKNIGLSIFIPLLLSATVENYIVNISFVFM PVCFCILCSIKNIKLVNNRK (SEQ ID NO: 1240)>orf00796MEKLVSIILPVYNVEQYIKNCLESIQQQTYSNLEVIIVNDGSTDKSVEYCEQICKID SRFSITHKENG GLSDARNVGIDKSK⑶YLIFVDSDDFVSQDMVSYLVSCMENNEADIAICDPVHYYSDRQNNDLNIFSPASNVKVYE TTEALCEMFYQKSFLVSAffAKIFKRELFDDIRFPVGKLFEDSA 頂YLLFEKCETIAYSDAELYAYVHRDNSITTK KFSDRDLDILEITNTIINHY⑶NLRVYTAAVSYKVSACFRILLNSPSGEKYKKVQKECLSYILQNWRNILFNNNV RLKNKLALISITIFNPFVKFIYSKVNRWE (SEQ ID NO 1241)>orf00797MNKYEERYQENLSKNDFYKLINKSYLSDKELQVQQVKAGIVLPPKAFETKLSNKLGLQKSLHGKGGVVD SNGNYIELSAQKAVGMRNRVYGPYKINYDNLPIRNEKVIYLNYFIKQWGHFLLDVVGRLWYPLLQDNDTKLVYTCYA GTETKIEGNYLEFLKLLGIDQSRLIMINCPTQFSEVIIPESSILPGGYYTKEYKQLFSSVVENIKLDKYDVNAKMIYCSRSKLGIAKSKEFGEDGIEGIFKQNGYTSVYMETMSLEEQIKTLLSAKTIVLTSGSLAHNLLFVNKDIDVFILNKT YRVNLHQFLINEISDATVRFVDIYRSPLPILYGYGPFLMDLTKPLANFLDDNEFVYEKGTVLSKKDYFKYYLKWLWS YRFFLFRLNGIKEGNSEFEKSFKIIRRYYKTGR(SEQ ID NO: 1242)>orf00798 MSKYKELAKNTGIFALANFSSKILIFLLVPIYTRVLTTTEYGFYDLVYTTIQLFVPILTLNISEAVMR FLMKDGVSKKSVFSIAVLDIFIGSIAFALLLLVNNLFSLSDLISQYSIYIFVIFVFYTLNNFLIQFSKGIDKIGVT AISGVISTAVMLAMNVILLVVFDWGLLGFFIANVCGYVIPCIYIVSRLRLWELFEIKIDKKLQWEMVYYALPLVL NILSffffVNNTSDRYIVTAIVGIQASAIISVAYKIPQILSTISAIFIQSWQISAIKIQEDKSDTTFVSNMLLYYNA LLLIIASGIILFVKPISNILFGISFYSAWELVPFLIISSLFNAISGCIGAIMGAKMDTHNIAKSALVGMIANIIL NIVLTFLMGPQGITISTLIASFLIFYMRKDSVKEINSETYRAIYLSWILLVVEACLLIYMDFIIGALIAMVINLF LLKDVIKPLYLKIFKRN(SEQ ID NO : 1243)>orf00799MIVLQYFKILARFVFMFLISAVLLPFKIKPNKIVFINFNGKGY⑶NPKSICEYLRTTYPDLDLVWLARD NEGFPDGVRVVKYGTFQAFYEQASSKVWVYNVRAFARILKKRGQIYIQTWHGASSFKLIEKQADLPINYVLEAKYDA RVTDIMISDSRKQTEEFQKYFWYSGEIFEVGMPRNDALFHYKEDYDKLNNIRKELSIHSDDYVILYAPTFRDDGDAS YLDINFERLLQCVEHGIKKKCKFLIRLHPNHSHLCNNISFNKNIINATFYSDMQELTLLADVLVTDYSSSIFDFMLL NKPYVRYVNDLEKYAELRGVSDTYYELPDSIIKTAEELYDLLPKKIENFDYDSIKKYRNEILCPIFNGTASENVGGR IIQEL (SEQ ID NO : 1244)>orf00800LKNNDLKIGSGAIHQISATLSQNSISGKILYCADPVVDDLYGSIVRSQIEEIGRVKEESCNYNTIAYAM NIAERAIATDIDCIVGMGGGRVLDVCKYASFISKRPYLSIPTTAANDGIASPVAVLKRQDDRPKSLGAAIPSMTLID IDVIASGPIQNIKAGIGDTISNYTALKDffELAVERGKDEMHGFAYLMSQNSLDALMKTKYNSITPDFIEVLVNSLVL SGIAMDFAGSSRPVSGSEHLFSHALDYYGSTRNLHGIQVALGTVAVLKLIENSVDTVVDYLQRFEVHINPKLLGIDE ELFIYCMQHATKMRSNRYTYLHEVDLSTDRLKQIYKELISEL(SEQ ID NO : 1245)>orf00801MKALILAAGLGTRLAPITNEVPKSLVPVNGKPILMKQIENLYQNNITDITIIAGYKSSVLTDAVTEKYP EINIIDNVDFKTTNNMYSAYLGKAAMGDSDFLMMNADVFYDASVIKSLLLHKAPNAIVTDLGIYIEESMKVVEKNGR LVEISKQISPEETLGASIDVYKFSYEAGARFFEKCKEFIEDKRELQMWSEVALNAILSEVEFVACPLEGRffLEIDNH EDLVAAEKLFA(SEQ ID NO : 1246)>orf00802MKLTNRVDYFGADISELQNKKLFLFDMDGTIYEEDRLFEGTLELLDYIHNIGGEYIFITNNSSKSVVDY VEKVNRLGIKAERDNFFTSAQATIVYIKENYPKSKVYCQGTKSLIKELSDAGIDVTEQVSADIDVVLVGFDTELTSD KIRNTCEILSTKDVPFIATNPDIRCPVSFGFIPDCGSICDMISKSVDRKPVYIGKPEPTMVDIVRKKLNYSLFETW I⑶RLYTDIMTGINAGVTSVCVLTGEATVNDIQQDSIKPTYTFKNVKEMWKGIV (SEQ ID NO: 1247)>orf00804MKGIILAGGSGTRLYPLTRAASKQLMPVYDKPMIYYPLSTLMLAGIRDILIISTPQDLPRFKELLQDGS EFGIKLSYAEQPSPDGLAQAFIIGEEFI⑶DSVALILGDNIYHGPGLSTMLQKAAKKEKGATVFGYHVKDPERFGW EFDENMNAISIEEKPEYPRSNYAVTGLYFYDNDVVEIAKSIKPSPRGELEITDVNKAYLDRGDLSVELMGRGFAWLD TGTHESLLEASQYIETVQRMQNVQVANLEEIAYRMGYISREDVLALAQSLKKNEYGQYLLRLIGEA(SEQ ID NO 1248)>orf00806MTDNFFGKTLAARKVEAIPCMLEFDIPVHGDNRGWFKENFQKEKMLPLGFPESFFAEGKLQNNVSFSRK NVLRGLHAEPWDKYISVADGGKVLGSWVDLREGETFGNTYQTVIDASKGIFVPRGVANGFQVLSDTVSYSYLVNDYW ALELKPKYAFVNYADPSLGIEWENIAEAEVSEADKNHPLLKDVKPLKKEDL (SEQ ID NO : 1249)>orf00810MTEYKNIIVTGGAGFIGSNFVHYVYENFPDVHVTVLDKLTYAGNRANIEEILGNRVELW⑶IADAELV DKLAAQADAIVHYAAESHNDNSLNDPSPFIHTNFIGTYTLLEAARKYDIRFHHVSTDEVY⑶LPLREDLPGHGEGPG EKFTAETKYNPSSPYSSTKAASDLIVKAWVRSFGVKATISNCSNNYGPYQHIEKFIPRQITNILSGIKPKLYGEGKN VRDWIHTNDHSSGVWTILTKGQIGETYLIGADGEKNNKEV LELILKEMGQAADAYDHVTDRAGHDLRYAIDASKLRD ELGffKPEFTNFEAGLKATIKffYTDNQEffffKAEKEAVEANYAKTQEIITV(SEQ ID NO 1250)>orf00813MILITGANGQLGTELRYLLDERNEEYVAVDVAEMDITNEEMVEKVFEEVKPTLVYHCAAYTAVDAAEDE GKELDFAINVTGTKNVARASEKHGATLVYISTDYVFDGKKPVGQEWEVDDRPDPQTEYGRTKRMGEELVEKHVSNFY IlRTAffVFGNYGKNFVFTMQNLAKTHKTLTVVNDQYGRPTffTRTLAEFMTYLAENRKEFGYYHLSNDATEDTTffYDF AVEILKDTDVEVKPVDSSQFPAKAKRPLNSTMSLAKAKATGFVIPTWQDALQEFYKQEVR(SEQ ID NO 1251)>orf00814LVNCEPLEAYRQLEEAELVGCffAHVRRKFFEATPKQADKSSLGAKGLAYCNQLFSLERDWEALPADER LQKRQEELQPLMEDFFAWCRRQSVLSGSKLGRAIEYSLKYKETFKTILKDGHLVLSNNLAERAIKSLVMGRSKRVQ WTLLA (SEQ ID NO : 1252)>orf00823MNKGLFEKRCKYSIRKFSLGVASVMIGAAFFGTSPVLADSVQSGSTANLPADLATALATAKENDGRDFE APKVGEDQGSPEVTDGPKTEEELLALEKEKPAEEKPKEDKHAAAKPETLKTVTPEWQTVEKKEQQGTVTIREEKGVR YNQLSSTAQNDNAGKPALFEKKGLTVDANGNATVDLTFKEDSEKGKSRFGVFLKFKDTNNNVFVGYDKDGWFWEYKS PTTSTWYRGSRVAAPETGSTNRLSITLKSDGQLNASNNDVNLFDTVTLPAAVNDHLKNEKKILLKAGSYDDERTVVS VKTDNQEGVKTEDTPAEKETGPEVDDSKVTYDTIQSKVLKAVIDQAFPRVKEYSLNGHTLPGQVQQFNQVFINNHRI TPEVTYKKINETTAEYLMKLRDDAHLINAEMTVRLQVVDNQLHFDVTKIVNHNQVTPGQKIDDERKLLSSISFLGNA LVSVSSDQTGAKFDGATMSNNTHVSGDDHIDVTNPMKDLAKGYMYGFVSTDKLAAGVWSNSQNSYGGGSNDWTRLTA YKETVGNANYVGIHSSEffQWEKAYKGIVFPEYTKELPSAKVVITEDANADKNVDWQDGAIAYRSIMNNPQGWEKVKD ITAYRIAMNFGSQAQNPFLMTLDGIKKINLHTDGLGQGVLLKGYGSEGHDSGHLNYADIGKRIGGVEDFKTLIEKAK KYGAHLGIHVNASETYPESKYFNEKILRKNPDGSYSYGWNWLDQGINIDAAYDLAHGRLARffEDLKKKLGDGLDFIY VDVWGNGQS⑶NGAWATHVLAKEINKQGWRFAIEWGHGGEYDSTFHHWAADLTYGGYTNKGINSAITRFIRNHQKDA WVGDYRSYGGAANYPLLGGYSMKDFEGffQGRSDYNGYVTNLFAHDVMTKYFQHFTVSKffENGTPVTMTDNGSTYKffT PEMRVELVDADNNKVVVTRKSNDVNSPQYRERTVTLNGRVIQDGSAYLTPWNWDANGKKLSTDKEKMYYFNTQAGAT TWTLPSDWAKSKVYLYKLTDQGKTEEQELTVKDGKITLDLLANQPYVLYRSKQTNPEMSWSEGMHIYDQGFNSGTLK HWTISGDASKAEIVKSQGANDMLRIQGNKEKVSLTQKLTGLKPNTKYAVYVGVDNRSNAKASITVNTGEKEVTTYTN KSLALNYVKAYAHNTRRNNATVDDTSYFQNMYAFFTTGSDVSNVTLTLSREA⑶EATYFDEIRTFENNSSMYGDKHD TGKGTFKQDFENVAQGIFPFVVGGVEGVEDNRTHLSEKHDPYTQRGWNGKKVDDVIEGNWSLKTNGLVSRRNLVYQT IPQNFRFEAGKTYRVTFEYEAGSDNTYAFVVGKGEFQSGRRGTQASNLEMHELPNTWTDSKKAKKATFLVTGAETGDTffVGIYSTGNASNTRGDSGGNANFRGYNDFMMDNLQIEEITLTGKMLTENALKNYLPTVAMTNYTKESMDALKEAVF NLSQADDDISVEEARAEIAKIEALKNALVQKKTALVADDFESLDAPAQPDEGLENAFDGNVSSLWHTSWNGGDVGKP ATMVLKEATEITGLRYIPRGSGSNGNLRDVKLVVTDESGKEHTFAATDWPDNNKPKDIDFGKTIKAKKIVLTGTKTY GDGGDKYQSAAELIFTRPQVAETPLDLSGYEAALAKAQKLTDKDNQEEVASVQASMKYATDNHLLTERMVEYFADYL NQLKDSATKSDAPTVEKPEFKLSSLASEQGKTPDYKQEIDRPETPEQILPATGESQSDTALFLAGVSLALSALFVVK TKKD (SEQ ID NO 1253)>orf00824LQIAQESSQDTDGINPPVVEEAMVFDRNDCLNQICGNIISLGIDAAFRTQVSNELIFIVVDFTRSCCN (SEQ ID NO 1254)>orf00826MLNLMWMKIFHRNRTFLFCFLGFKVDVISIINARIVRR (SEQ ID NO : 1255)>orf00827VYNSQALRQIVVVGSIDHLFKRHSSICEIFGLRKRWLSFL (SEQ ID NO : 1256)>orf00830 MTSIIFSAKDIFEQEFGREVRGYSKVEVDEFLDDVIKDYETYATLVKSLRQEIADLKEELTRKPQVSSA PSPSHPDPIDVAASSSMTNFDILKRLNRLEKEVFGKQILDNTDL(SEQ ID NO : 1257)>orf00854LISIKHFFffLPLSKKMIIDIIVNKNPDRFCMIEKVKKTMAENR (SEQ ID NO : 1258)>orf00858VNIDSSEFYISHITDGIFDSFLDSNRYLRNFYSVLKVEIDICCEFFVHVFKINATAE(SEQ ID NO: 1259)>orf00859VNPLYLCSSDSNDFFKYTWGDNDFAKLFFNSHRMTSF (SEQ ID NO : 1260)>orf00887LAQISILHFDFLSIDKHSHTVFNTLRKSLQTTLALSATSKQCFEQLAASFLVCSLIFIEYKV(SEQ ID NO 1261)>orf00897MLYVGIDIAKNKHDVTALNVPGKTVLKPLTFSNNKAGFELLDLSLRQLNQDCLIALKLLSDPNREQFQ HDNRQVDLKILARHIHRLKKKQSDWKVQYTRCLDIIFPELDKIVGKHSEYTYQLLTRYPNPQKRIEAGFDKLIEIK RLTASKIQDILSVAPRSIETTSPAREFEIIEIIKHYKRLIDKAETCVNDLMAEFNSVITTVTGIGGRLGAVILAE IRNIHAFDNPAQLQAFAGLDSSIYQSGQIDLAGRMIKRGSPHLRWALIQAAKACARFSPAFKAYLKTKLEQGKHY NVAIIHLAKKLIRTLFYILKKSCHLTNKK (SEQ ID NO : 1262)>orf00900MDTKSSCLITTGRNDSPSTCLPRVASNNDRFSSEFRIIPDFHCSKKGIHVNMDDFS(SEQ ID NO: 1263)>orf00903MMSIREQDLKDIGAIIKYKNFHSPFDTFKYLKDMGFDTIDLSVLLEGFSYAYGMDWLEKFFKENQDKLR EFY (SEQ ID NO : 1264)>orf00909[2967]MIPLYRTDNDITKFFTKIRNGHLAKTAGGLDDKFHEANASTSKAFDRQGVGEVNDIRDSAGSQELRIND KRKTENILFLEIRVRIFRVPHPNDSFFSSHFLG(SEQ ID NO: 1265)>orf00910VLSQGDKDITILDAGLLKNGKIGPVTKDTNDIKATD匪IENSFVLLNQQNIMLFCNQGATEGKTNFSPS DKDNFHNKTYFFMM (SEQ ID NO: 1266)>orf00915MKIKEQTRKLAAGCSKQCFEIVDRTDEVSSKHGFEVVDETDEVSNHTYGKAKLTWFEEIFEEYKMMGKA GQLVFFDVYRLVRQVS (SEQ ID NO: 1267)>orf00942LVEIVRGGSPRPIKDYLTSEVDGINWIKIGDTEKGEKYINNVKEKIKKSGLNKTRFVKKGTFLLTNSMS FGRPYILNVDGAIHDGWLAISNYENSLNKDYLFYILSSNVVYSQFLSLISGAVVKNLNSDKVASILIPLPPLSEQQR IIEAIESALEKVDEYAESYNRLEQLDKEFPDKLKKSILQYAMQGKLVEQDPNDESVEVLLEKIRAEKQKLFEEGKIK KKDLDISIVSQGDDNSYYGNIPMNWVVIKIKDIFSMNTGLSYKKGDLSINNKGVRIIRGGNIKPLEFSLLDNDYYID TQFISSEQVYLKHNQLITPVSTSLEHIGKFARIDKDYDGVVAGGFIFQLTPFESSEIISKFLLFNLSSPLFYKQLKA ITKLSGQALYNIPKTTLSELLIPLAPFEEQELITQKVEKLFEKVNQLWK (SEQ ID NO : 1268)>orf00963VDRTDEVSSKHCFEVVDTTDEVSSKHCFEVVDRTDEVSNHTHDKPTLTWFEEIFEEYHSPFHN (SEQ ID NO 1269)>orf00964LDNIHIVLDSLNAVSGIQDFICDGLAIFCDQITSGCSSCK (SEQ ID NO : 1270)>orf00979MKSTLGIISVGLVITYILQQVMSFSRDYLLTVLSQRLSIDVILSYIRHIFELPMSFFATR RTGEIISRFTDANSIIDALASTILSLFLDVSILILVGGVLLAQNPNLFLLSLISIPIYMFIIFSFMKPFEKMNHDVM QSNSMVSSAIIEDINGIETIKSLTSEENRYQNIDSEFVDYLEKSFKLSKYSILQTSLKQGTKLVLNILILWFGAQLV MSSKISIGQLITFNTLFSYFTTPMENIINLQTKLQSAKVANNRLNEVYLVESEFQVQENPVHSHFLMGDIEFDDLSY KYGFGRDTLTDINLTIKQGDKVSLVGVSGSGKTTLAKMIVNFFEPYKGHISINHQDIKNIDKKVLRRHINYLPQQAY IFNGSILENLTLGGNHMISQEDILRACELAEIRQDIERMPMGYQTQLSDGAGLSGGQKQRIALARALLTKAPVLILD EATSGLDVLTEKKVIDNLMSLTDKTILFVAHRLSIAERTNRVIVLDQGKIIEVGSHQELMQAQGFYHHLFNK(SEQ ID NO 1271)>orf00981MTSYKRTFVPQIDARDCGVAALASIAKFYGSDFSLAHLRELAKTNKEGTTALGIVKAADEMGFETRPVQ ADKTLFDMSDVPYPFIVHVNKEGKLQHYYWYQTKKDYLII⑶PDPSVKITKMSKERFFYEWTGVAIFLATKPSYQP HKDKKNGLLSKLPSSDFQTKISHCLHCSLKLIGHYYQYRWFLLSPRNLG (SEQ ID NO : 1272)>orf00984MDTKMMSQFSVMDTEMLACVEGGGCNWGDFAKAGVGGAAVVAALGCAAGGVKYGKILGPWGAAIGGIGG AVVCGYLAYTATS (SEQ ID NO : 1273)>orf00988MKKKILIIFVLYLIMSIFLYPLRESIWYNLFYTIAYMIAVMIYFSLIKKKEKK(SEQ ID NO : 1274) >orf01008LNCKGNDHPKEFHNPNNRFDKKNSKKTKKNFILSPLA (SEQ ID NO : 1275)[2987]>orf01009MKIKEQTRKLAAGCSKQCFEVVDRTDEVSSKHRFEVVDRTDEVSSKHRFEVVDRTDEVSSKHRFEVVDR TDEVSNIYTAR (SEQ ID NO : 1276)>orf01017MHSQTFQFLLMTDKTSLLHRKHRSFIRNIHSKFLILFDLLCGILSRNDSNHNPIS(SEQ ID NO: 1277)>orf01021MSDVKEEVSSLSEKQLRQIDVEYAELNDSDIIERLAYLEINNNEKRIVISDIEPTKEIMSVSDQIFEI QKNFQKIK匪FELFISDVSDFLSIKNKLESKELEIEEADVNRFMIHLLSSGKLFVDFNENQIKQKYSKDSEEFDCI HGFASYQYDTNFAYRFCHSLRNYSQHTDLPINEVKAVSPDDETVIIDFYIDLDYLLNSNFKffKKLKGELIKLNQE TSKIDAIALVKEYFNALTELYGNYNKLFLKLNHNTLVDIKSKLESLKLKHSRYYISKISKYDLKYNPGNYTMSPL A AFAEIEEIYIELSKIGLVKIVNKSN (SEQ ID NO: 1278)>orf01025MSKHPHYELLNLIGYGLAKFDKLFIKEFQCFSKSEFYRYVVSLGIAETTGVVKNRMDLFD PYFDNNRKGWWQKAEVYRFRKDLIDMMFGNEDVHSYAEIVKMLLASEGKKTGITIVEKPIVRTKFKRLQETGMEAEN YFILHFDKEEKFQGGQLTDARLYGDGYDFQVDVQEYSYLAEVKGIRKSKGRVRLTAKEFEKVKEFQSDFILSLVTNL DDIPKLVLIDNPLKHFEFKKNIIKNEIIEYRSVEDLY (SEQ ID NO: 1279)>orf01027MFIAEFTAILLNEFPVALDSLVFMGFSMKLIHDLDTHTTHSTAKMLYNMKAIKNDFSIRE(SEQ ID NO 1280)>orf01049LKHLFCHFNPLWIDEIIRLAYKDQDTKDVKSKVKIGN (SEQ ID NO : 1281)>orf01077LCCNRHIANLDLEFISYHLGQVGFDTRISTGLGIFVTKIGNVLFDTDNQFASFLNVCDTCISLDWFGSS KAEKANQ (SEQ ID NO : 1282)>orf01095MKEIAFDAFYQLYQNDQLSLVDVREVDEFAALHLECAHNLPLSQLADSYD(SEQ ID NO : 1283)>orf01098MCLICQRIELIKAGQNPYFVKELETGYWI ⑶ YQYFKGYTLFLAKDHVTELHHMETSVKLRFLEEMSL VQEAVAKAFEAEKMNIELLGNGDAHAHWHLFPRRAGDMKSHGLNGRGPVffffVPWEEMAAEDCQVQSPELEEMIKIL SHELEKYLA (SEQ ID NO : 1284)>orf01099MKKRYVILSGLLALTLAACSQEKTKVEENTQKTEQSSQPEGTVGSKSQASSQKKAEVSNKGSYYSIQGK YDEIILANKRYPLSKDYNPGENPTAKAELLKLIAAMQAEGYPISDQYSGFRSYETQAKLYQDYVNQDGKEAADRYSA RPGYSEHQTGLAFDLIGTDGDLVTEEKAAQWLLDHAADYGFVVRYLKGKEKETGYMAEEWHLRYVGKEAKEIAASGL SLEEYYGFEGGDYVD(SEQ ID NO : 1285)>orf01104MKTKEQTRKLAAGCSKHCFEVVDRTDEVSNHTHGKATLTWFEEIFKEY(SEQ ID NO : 1286)>orf01105MDFFFMNEVKEQVLFRDNHSEHIFWIEGVSDFMIKVNTALW (SEQ ID NO : 1287)[3010]>orf01109VCFLGFQTILANPSKPQRQLPFLIFILDFFNYKHHKFLS (SEQ ID NO 1288)>orf01124MEELVTLDCLFIDGTKIEANANKYSFVWKKTTEKFSAKLQEQIQVYFQEEITPLLIKYAMFDKEQKRGY KESAKNLANWHYNDKEDSYTHPDGWYYRFHHTKHQKTQTDFQQEIKVYYADEPESAPQKGLYMNERYQNLKAKECQALLSPQGRQIFAQRKIDVEPVFGQIKASLGYKRCNLRGK(SEQ ID NO : 1289)>orf01126MHIHYNTNQTTLPLEISSFLPQDHLVFTIEKVVNTLEDCHFHAFYHAFDRLSYHLKMLVSTLLFAYSQG IFSGRKIEKffKS (SEQ ID NO : 1290)>orf01129LRLWVIFVMKVIKSYDTLNDYYRKLFGEKTFKVPIDAGFDCPNRDGTVAHGGCTFCTVSGS ⑶ AIVAP DPPIREQFYKEIDFIHRKWPDVQKYLVYFQNFTNTHEKVEVIRERYEQAINEPGVVGINIGTRPDCLPDETIEYLAE LSECMHVTVELGLQTTYEATSDLINRAHSYEL(SEQ ID NO : 1291)>orf01131VETVKRLRKYPKIEIVSHLINGLPGETHEMMVENVRRCVTDNDIQGIKLHLLHLMTNTRMQRDYHEGR LQLMSQDEYVRVICDQLEIIPKHIVIHRITCDAPRDMLIGPMWSLNKWEVLNSIEMEMRRRGSVQGCKAVKQEFEN EKTT (SEQ ID NO : 1292)>orf01143VQVCVFTNFCFFHCFSSLANCRLFNLRGICLPCISYQ (SEQ ID NO : 1293)>orf01152VFKKDRFSIRKIKGVVGSVFLGSLLMAPSVVDAATYHYVNKEIISQEAKDLIQTGKPDRNEVVYGLVYQ KDQLPQTGTEASVLTAFGYLS⑶ILKTLGLDTVLEETSAKPGEVTVVEVETPQSTTNQEQARTENQWETEEAPKEE APKTEESPKEEPKSEIKPTDDTLPKVEEGKEDSAEPAPVEEVGGEVESKPEEKVAVKPESQPSDKPTEEPKVEQVGE PVEPSEDEQAPTAPVEPEKQPEAPEEEKAVEETPKPEDKIKGIGTKEPVDKSELNNQIDKASSVSPTDYSTASYNDL GPVLETAKGVYASEPVKQPEVNSETNKLKTAIDALNVDKTELNNTIADAKTKVKEHYSDRSWQNLQTGVTEAEKVAA NTDAKQSEVNSETASLKTAISRLNTDKVELENQLKIAQGKTETDFSMESWTVLSTAKNKAQEVKDNGTATQEQINEA EKSLKTALADLSVDKTALGSAIDTATKKNKENYTNQTWAELETALTAAKSVNTNESKQSDVNEAAEKLTATMEKLVE LSEKPRLTLSIEKRDIDRKATVTYTLENPANTQIKSITATLKKGEEVVKDFVLTEENLKTNHLTALFEKLDYYKEYT LSTDMVYNRGNDDETESISEELIQLNLKKLELKDIQTVSLMKFENGQESQVTHLSDKPTDLSKLYLKVTSSTSKDAV LAVSSIEEEIIENKKIFKIHADTPELVVRKKDGSLSKGFDYYMERVIPHD⑶IYYDFKDLISAMTSNPTGTFILGRD ISSRNVKPDGNGKSYIKGEFKGKLLGTNDNVRHSIFDLEYPLFDTIKSGWKDIDFKHVNMVFPDSNQ⑶NVATIAR VIKDKTKIENVNVEGYLEGRDHVAGLVNNLEGNSEIENVSFTGKIKSKGGNSITAGIAGRNILSRVKRAYVNADIEV HRSSNSSMLVAVNGINADASGGWGTWGRLTESVAKGTLETKQGGQAGGASSTVWPYGAIDNVVSYAKVTKGKELFGS DGDLNYDWFMKKISNIFGVQGISS⑶SGSDSKFTRISEEEANQKVASYNITAPNLMSDSSLLVDRLNESWKNTDQFE SIQDYQAQNQLIYQNLTKFTPYYNKEFIVHEGNALTPEQEILKTKKIKSIVGLKGTEFVVDGSDIDTIMLHFEDGSQ KRYKVTSTGKFSITNLPEYQVEDLNVVYTSEHIVHPLDSSLINNLVEELKKVELYTESTYQVLGIDKDNANKLNRTK RLFLDESLDAVKTQLPTFVKTMFENEWLHINGESSGAVAALRQKIMDNKTAILLALTYINRYYDVKFSDYNIKKLML FKPTFHGEKIDLLDRLIRLGSSGENRLKGSENAETFKQLFASETKQKDLVTYLDYNRSLLTNYQTTGEWFKETTKDY IQFEERPSLVEEIKDAKYRVYDNLTAPYYQGYILPLLTLKNTHLAILSNYSTMTFVSREKRPNWKNEDFDKWVKYVATAHRNHVDTffYKILPDNIKGKMVKENVTAVffEGLSIPGSEWVDQNAVDRKGRDYAPAREFFNLVGGPMGGWYAYHGY GAHAGGRNRVNYEVFDVLSEYGISVFTHELTHVNDTWIYLGGYGRRENMGPEAYAQGLFQSPVPGQPGWGALGLNMA FERKNDGDLIYNASPTQFENRKELDSYMKNYNDTLMMVDYLEGDAVISKGKEAITKWFKKVEPKVVSQTAQYDTVRQ LTAEEKEKLSVSSVDDLVDQGLMSDRAVGNNTYNPADFETSYIAIDYMTGIYGGGKNSVGSPGALMFKHNTFRMWGY YGFEEGVLGYASNKFKQASRDEGHAGLSDNFIISKISKGEFLTMEAFKKGYFKKVVEELKTKGIRPVTINQKTYSTF EELQEGFKQAVERDLKKNQLDERETRNFKFQVFRQLLQQTDSFKTSIFR (SEQ ID NO : 1294)>orf01156 MKSKIVLGASLAIATLSLVSLVEIEGLSPFLIENVSANTHSANKVINHKVSIYLENADEGKGLTVNFST DSVSPNLFDEFEKKSGITITTMLVNAKTGEVVEKRLTPSVFLRSNDLTSGTISSFIFSEYPDGEYKYVVSKGDFIDP KTQFKHQYRGESPVFRIRNRKYVELGTTDKKLDERRDNSVYKDGVVEHKVNLSLTSYQGGNGVTAIFSTDSVNSNLL NSFGEKAKKVLIRSKLINVKTGEVIDETFSPKVSLTSKILKSGSTAVFYFIDLTDGEYKYVAYESQQYTDPQTTLTH QYRGESPIFSIKDGKFSGLVSASKPDENPKPTPKPDEKPKPSAPQQEKTKPTVQSGWVGSSYYQNGKKVTSKWIFDK KYNSYFYLDASGNYVQNAWVGNYYLKSGGYMAKSEWIYDKNYGSYYYLTSEGSYARNTWSGNYYLKSNGKMAKSEffV YDSNYKSYYYLTSEGSYARNTWVGNYYLKSNGKMAVNERTPDGYRVDGSGKWVK (SEQ ID NO: 1295)>orf01157MSACTVCAEKGRTPDLSIVDNVPIVENAKAHENNFFYSSDITYYPIF(SEQ ID NO : 1296)>orf01158MAKYYIILPKDAEIYKTWRGTVNIPIIDATKTTPELSYFKEDHRNYIANENKSGANYIEWKGTVEEFKE AIKKLTDKKSTTATPKKDEKPTPKPDEKPKPTPTVQSGWVGSSYYQDGKKVISKWIFDKKYNSYFYLDASGNYVQNA WVGNYYLKSGGYMAKGEWVYDATYQAffYYLTSDGSYAYSTffQGNYYLKSDGKMAVNEffVDGGRYYVGADGVffKEGQA STASSSNDSNSEYSAALGKAKSYNSLFHMSKKNVCIDN (SEQ ID NO: 1297)>orf01179VSRWDGHSDKGEAPAGKTSYAWIWTKWGEQVAFYCDYD (SEQ ID NO : 1298)>orf01193MKSKKGGELRIAVF⑶KKPFGYVDNDGSYQGYDIELGNQLAKDLGVKVKYISVDAANRAEYLISNKVDI TLANFTVTDERKKQVDFALPYMKVSLGVVSPKTGLITDVKQLEGKTLIVTKGTTAETYFEKNHPEIKLQKYDQYSDS YQALLDGRGDAFSTDNTEVLAWALENKGFEVGITSL⑶PDTIAAAVQKGNQELLDFINKDIEKLGKENFFHKAYEKT LHPTY⑶AAKADDLWEGGH (SEQ ID NO: 1299)>orf01194MKLFKPLLTVLALAFALIFITACSSGGNAGSSSGKTTAKARTIDEIKKRR(SEQ ID NO : 1300)>orf01231MYQDEAGFGRISKLGSCffAPIGVGPHVHSHYIREFHYCYGAVDAHTGESFFLIAGGCNTEWMNAFLEEL SQAYPDDYLLLVMDNAIWHKSSTLKIPTNIGFTFIPPYTPEMNPLNKCGKRFVNVDLRIRPFELWKMS (SEQ ID NO 1301)>orf01233MVTATTCFLKERVEFELLIFFYISPNRCLITVYSVLNL (SEQ ID NO : 1302)>orf01234MDTPDENGYVADDYRITYLEAHIKAMRDAIYKDGVDLLGYTTWGCIDSVSAGTGEMNKRYGFIYVDRDN VGNGTLKCSKKKSFYffYMSFIAMV (SEQ ID NO: 1303)[3042]>orf01255[3043]MFLGMIGNISIILQFFGITIIVKIDNQARAIDFFKHDKSSF (SEQ ID NO 1304)>orf01257MFSLNFFDDSVFLSIKIAHKGCFQLLDMTNPNFFNKFFLAQASDQLLHFLSWNIEL(SEQ ID NO: 1305)>orf01266MTEPDFWNDNIAAQKTSQELNELKNTYNTFHKMEELQDEVEILLDFLAEDESVHDELVAQLAELDKIM TSYEMTLLLSEPYDHNNAILEIHPGSGGTEAQDW⑶MLLRMYTRYGNAKGFKVEVLDYQA⑶EAGIKSVTLSFEGP NAYGLLKSEMGVHRLVRISPFDSAKRRHTSFTSVEVMPELDDTIEVEIREDDIKMDTFRSGGAGGQNVNKVSTGV RLTHIPTGIVVQSTVDRTQYGNRDRAMKMLQAKLYQMEQDKKAAEVDSLKGEKKEITffGSQIRSYVFTPYTMVKD HRTSFEVAQVDKVMD⑶LDGFIDAYLKWRIS (SEQ ID NO : 1306)>orf01267MLQSNQVQNFHHSSFDITAIFPDYFHSVSNIFIDSFLff (SEQ ID NO : 1307)>orf01299MQVIKRNGEIAEFNPDKIYQAILKAAQTVYVLTDDLRQNLAQVTKKVVLDLQEAKVERATISMIQSMVE HRLLGAGYITIAEHYISYRLQRDLERSGY⑶HIAVHLHFEQIR(SEQ ID NO: 1308)>orf01305MKLKLCIIGFFFCLIATIGLVTISDTEIPIPLPIDGAFSIQGKSNLSNNEIYEMVRDLSKTEKVTIYKP IVQSSGQLKYVNFDDVNNEQLKSAPIVGMYYTLGKMDVDSLKPLTMTGLQTVYMAYPWYIGGILQFTGTLRILLMGS IYLTLLVVLFVVRTRQIKEGVIRRSLGLPIYDLRREYGISLIFELIMMALLMISYSSFLGNGFFTYSSKLFFSLLLT NFILFQIIDLlTFVLFffLTIQIEKPIEIIKNKAKNKLIFVVffLAIISIIILVSGVFLQETKSSQSSINIQIQNLVPff DTVKDWRRIEFLGIESNSTKNREVNDSDGQYLQIVAALKNLDFLYIERSSAYVPDFMKTSHVIENFSKQLENDGITN PEINKELIYINQTGANLQNKVNGTNYHLLDNKIATIYIPEKWKENQKSIENTVVAEQFIGTNYTREQLAVQIIPDGE KIFYFNEDADNNLKMKDILPLANVADSKDNIVVVLDTDKMMENNKFSLASNILYKSLFSPEAVKKINEMTVLLNFSM NPVDVYQIVKLKIQSLEHQILLSQILQKIIYSIVFILIYQYVQLFITLKQNEYVKKIILGLSKTYIAISSLKYFMMT ITMVILFTFLMTGQIELLYIGAASLLVLMLSIIMSFRKLSESYTKILKGDES(SEQ ID NO 1309)>orf01306MTIDLLNVSKSFGSKKIFTDLNLIFESGKSYALIGGSGSGKSTLLNIIGRLEKIDSGNVLVDKQDIWK IKERTFFKNTVGYVFQNYSLIDNKTVYDNLSLITKDKKTITDVLEKVGLSSDYLHQKIYELSGGQAQRVAIARMLM KPRKIILADEPTGALDGEIGKEIIRLLLNETAEDKYVIIATHDPAVYNEVDVIIDMKDIGYKV (SEQ ID NO 1310)>orf01307MKKKIYIALIFVTGVLAIFFFGKQMITKENINKPTVELTIYTLSSSDTEKWNKVRQVETEEAIYFITV KEVSSSEEVFSNIIANGAATGFGVREEEVKKFNNGL⑶TIEDSKHNKLIEIEFFTFSDDGAGFWANFDYGKEELN SQKKDIKELYKKIYESFKEKNK(SEQ ID NO 1311)>orf01317MKIKEQTRKLAAGCSKHSFEVVDETDEVSSKHSFEVVDETDEVSNHT(SEQ ID NO : 1312)>orf01324 MELFKTWKKNMVLYGLKSQIGTVYRNNDRTTSFYDVGNFLYLAGELDSRFWEDFVRKYGLDYKIIISENTNWQDFLHRKVGLNSFTRYSFKDKANFQVEFLNNLVTHLEEGYNIVPIDNHIYNCFSTEEWSQDLQ⑶FESYQDFVL KGGFGFVILKNNELIAGISSGLVYRKAVEVEVATRPNEQGNGFAKKLGAAMILESLNRDMFPLWDAHNEASKKVAEF LGYELSEPYEAFELEEILI (SEQ ID NO 1313)>orf01369MKVIDQALLEKVIIERSRTSHK⑶YGRLLFLGGTYPYGGAIIMAALAAVKSGAGLVTVGTDRENIPALH SHLPEAMAFSLQDQQLLKEQLEKAEVVLLGPGLRDDAFGEDLVKQVFAGLRQNQILIVDGGALTILARTSLSFSSSQ LILTPHQKEWEKLSGITIEKQKEDATASALTSFPQGTILVEKGSATRIWQAGQSDYYQLQVGGPYQATGGMGDTLAG MIAGFAGQFKQASLYERVAVATHLHSAIAQELAQEQYVVLPTEISNCLPKVMKRYV (SEQ ID NO: 1314)>orf01376VLDSKEELKESENDAPKLETPLREEPRLAPQTLPEASEVLENKREESKVEITEPAQADDIRKVVGEL AKDISITKLYMTGHSLGGYLAQIAAVEDYQKYPDFYNHVLRKVTTFSAPKVITSRTVWDAKNGF(SEQ ID NO
1315)>orf01404MGRKPKKRPEERTELEHLQAENEYLRAENAILKKLRELRLKEEKEKEERQKLFKN(SEQ ID NO:
1316)>orf01417VVLSTSAILVACGKTDKEADAPTTFSYVYAVDPASLGYSIATRTSRTDVIGNVIDGLMENDKYGNVAPS QKDYDLNSTGWAPSYQDPASYLNIMDPKSGSAMKHLGITKGKDKDVVAKPGLDKYKKLLEDAVSETTDLEKRYEKYA KAQAWSTDSSLLMPTASSGGSPVVSNVVPFSKPYSQVGIKGEPYIFKGMKLQKDIVTTKEYNEVFKKffQKEKLESNS KYQKELEKYIK(SEQ ID NO 1317)>orf01421LNFDFFIFLAHFIPLFTFSILQENPKTSKKKLYIRLL (SEQ ID NO : 1318)>orf01428MRLSMKLIHDLDMHTTHSTAKMLYNMKAIKNDFSIRE (SEQ ID NO : 1319)>orf01442LIRIIRNIYRSGEGNTSVFQSFIDQINSNQFCYGSNFDRLRCILLIENFTSICLNSNRMFSGNGKILSN SSRSTP (SEQ ID NO : 1320)>orf01453MSNYRRTSKPKTEHIKKGFTVFQKTITTIGSILGLITAGITIMNALDNNNKNTKKEPTTSQTTTFVK EIQKESPQENTTPNKENNTSQEKTQQEETPKSSVKEEKKEDQKTATQDSTTPATSKPATENEKQPNTPTSENNTQ (SEQ ID NO 1321)>orf01457MNQSYFYLKMKEHKLKVPYTGKERRVRILLPKDYEKDTDRSYPVVYFHDGQNVFNSKESFIGHSWKIIP AIKRNPDISRMIVVAIDNDGMGRMNEYAAWKFQESPIPEQQFGGKGVEYAEFVMEVVKPFIKHKTGWFDGMMTTGCS MGAYHALNFFLQHPDVFTKVIALSGVYDARFFV⑶YYNDDAIYQNSPVDYIWNQNDGWFIDRYRQAEIVLCTGLGAW EQDGLPSFYKLKEAFDQKQIPAffFAEffGHDVAHDffEffffRKQMPYFLGNLYL (SEQ ID NO : 1322)>orf01466MSSIHTKNSSLKSKSRFNEMF⑶PLNNNKKFAVKTGQQCFKFSSGKFLDKHDRVFEGYPAYGGNGIAWK SRKYLIDNPTIIIGRVGAYCGNVRTTHGKVWISDNAIYIKEFKNSDFNLVFLLELMKVIDFSKFADFSGQPKITQKPLENQKYILPPLALQNEFADFVALVDKSQFACEIAIKVWRNSLKFSII (SEQ ID NO : 1323)>orf01476 [3083]LVYAPFSFNILLDYITFDFKILLFSVFLAINRFHNDFIQFLL (SEQ ID NO : 1324)>orf01479MSEYSGLSFFEVALAEFLDIVSAVYLEDADGIIVNLWGILDK (SEQ ID NO : 1325)>orf01490MEGVAKGRIGRKKNNGIDNRCCHKKRNGRVTWNLFFQKTIDDGDDSTFTRREKYTDKGPKKDSPPTISR EKMINLVRCDINFNQP (SEQ ID NO: 1326)>orf01493VDKTDEVSSKHCFEVVDRTDEVSSKHCFEVVDRTDEVSSKHCFEVVDRTDEVSNRTTVRRS (SEQ ID NO 1327)>orf01495MTEFMSDNFPKNLHTQFLINLGIKIQMPIFGEKSPTCRT (SEQ ID NO : 1328)>orf01503VVIGVASATTNIWIIFLSGFTAILAGAFSMAGGEYVSVSTPKDTEEAAVSREKLLLDQDRELAKKSLYA AYIQNGEFKTSAQLLTNKIFLKNPLKALVEEKYGIEYEEFTNPWHAAISSFVAFFLRSLPPMLSVTIFPSDYRIPAT VLIVGVALLLTGYTSARLGKAPTKTAMIRNLAIGLLTMGVTFLLEQLFSI (SEQ ID NO : 1329)>orf01535MSFKNNWIDKEGRVFIYFTVEEIMKRRNISKPTAIKTLDELDIKKGIGLIERVRLGLGKPNIIYVKDFM SIFQVKENDLQKSKNLTSEVKDFNLRSKENELQEVKNLDSNYIENNKSKYSKREYSFGENGLGTFQNVFLAAEDI (SEQ ID NO 1330)>orf01543LLHIRVCKTFDRIPYCMLALFLSKSIGLTILLHKVKTVIFIDDQSNDKTCKICIHISFFRIKLSQQCQL SFSVYF (SEQ ID NO : 1331)>orf01547MTQEDALIVISHIKVLSIVPNRCLKPLDKTFSLYNffIFLSQKYILLQANFLKISRVQLQ(SEQ ID NO 1332)>orf01552 VTTHDEPVYEKHGVLHYAVANIPGAVARTSTIALTNVTLPYIEALAGKGFAQAISEDEGLRQGVTTYQG YLTSLPVAQGLNRDYTDINDLV (SEQ ID NO: 1333)>orf01553VFFIDGFIVRCHTVSCFDNATLVNSNVNDTEPGRICLTISSVTNSGAFAPGMRMAPITTSASLTLASML NELDIRV (SEQ ID NO : 1334)>orf01555LSTKTK⑶AGSMCTDDTITDDSYFSFGTPGTPPGRTPEPPACLVRK(SEQ ID NO : 1335)>orf01556MLIGIPKEIKNNENRVALTPAGVHSLVSRGHRVLIETNAGLGSGFTDADYQKQGAEIVATAGEAffAA ELVVKVKEPLNSEYGYLRDDLLLFTYLHMAAAPELADAMLAAKTTGIAYETVRDNQGQLPLLVPMSEVAGRMAV (SEQ ID NO 1336)[3108]>orf01576MASRNVLSMEPKFLLAGHFKGQFLILKIVSSDIDDGFAIAC (SEQ ID NO 1337)>orf01577LSSADKTCLNQFFTDFSDFFQSSLVEDGFYTFQIENSGFGFFNQISQVFDSFFEFLIPFKIALGILVGS QSLIKRNHDRLVGIVVV (SEQ ID NO: 1338)>orf01578VSVFLKFIFNTTNQFTGLLFDAVALSLILIVGVQQIRKICKRLSHLICKRNWTEGSLSQAWLGFLIEKI SESGKFFTNQYPFQFICSIASQTLKEALKIFCC(SEQ ID NO: 1339)>orf01579 MVSNLVFIGNCNFHNTVIFHLLNRLNQGPLQILSQNHDKGRRLSWIFKSRLGQLNASKNWMGRKEQAMA LAIAADLQDQLLFKRLIDFLDATIH (SEQ ID NO: 1340)>orf01599LLYNPVEKTRVHIKKGIGKLQYLFTRLFYLIFVSTDYISYGSSSEG (SEQ ID NO : 1341)>orf01630MRSYITLICNLNNNLFCLNSFFLTNLVWSQIFSLLSVFITVYI (SEQ ID NO : 1342)>orf01631 LLEITLKSPYQFAHILFQSTIVPHGGHYHFIPESDLSAGELAATYVFNPNDIVRDTCDAYIVRHGDHYH YIPKSSLNNPPSHSNTEEVGSSSSSVLSNPSLHVHHEEEDGHGFDANRIISEDSEGFVIPH⑶HNHYIKVQTKGYEA ALKNKIPSLQSNYQPGTFDEKAVLAKVDQLLADSRSIYKDRLS (SEQ ID NO: 1343)>orf01664MARLEPAKIAKIVLGILLYIIDLIKSSFVLPIPKAAKKSLILISFVPSFNDKNIVIRRPRQITKIMPRF ICFLFRIFACIS (SEQ ID NO : 1344)>orf01680MELSAIYHGPESEYAYLYKDKKLHIRIRTKK⑶IESINLHY⑶PFIFMEEFYQDTKEMVKITSGTLFDH WQVEVSVDFARIQYLFELRDTEGQNILYGDKGCVENSLENLHAIGNGFKLPYLHEIDACKVPDWVSNTVWYQIFPER FANGNALLNPEGTLDWDSSVTPKSDDFFG⑶LQGIIDHMDYLQDLGITGLYLCPIFESTSNHKYNTTDYFEIDRHFG DKETFRELVDQAHHRGMKVMLDAVFNHIASQSLQWKNVVKNGEQSAYKDWFHIQQFPVTTEKLVNKRDLPYHVFGFE DYMPKLNTANPEVKNYLLKVATYfflEEFNIDAWRLDVANEIDHQFWKDFRKAVLAKNPDLYILGEVffHTSQPffLNGD EFHAVMNYPLSDSIKDYFLRGIKKTDQFIDEINGESMYYKQQISEVMFNLLDSHDTERILWTANEDVQLVKSALAFL FLQKGTPCIYYGTELALTGGPDPDCRRCMPWERVSSDNDMLNFMKRLIKIRKYASVIISHGKYSLQEINSDLVALEW KYEGRILKAIFNQSTEDYLLEKEAVALASNCQELDNQLVISPDGFMIF (SEQ ID NO : 1345)>orf01688MGQEIKLIRKQFRITRQEEKQIKEMMREQKVDSFSEFLRQNLLKKNYQDRIFESWFSLWQSQKFEQISR DVYEVLVVARENHQVTQEHVSILLTCVQELIAEVNQVQPLSREFREKYMG(SEQ ID NO 1346)>orf01689MVYRYRTNLKKVFLTDPELHQLNERIAKSNCQNFSVYARKVLLNP匪SFVTINTDTYDQLVFELRRIGN NINQIARAINQSHLISQDQLQELSKGVGELIKEVDKEFQV(SEQ ID NO: 1347)>orf01690MVVTKHFATHGKKYRRRLIKYILNPDKTDNLKLVSDFGMSNYLDFPSHTEMVEMYNVNFTNNDKLYESRNDRQEKHQQTIHAHHLIQSFSPEDNLTPEEINRIGYETMMELTGGRFKFIVATHTDKDHVHNHILINAIDRNSDKKL IffNYALERNLRMISDRISKMAGAKIIEKRYSYRGYKKYRESSHKFELKQRLYFLMQQSK (SEQ ID NO: 1348)>orf01691MMTDRAMTKPIRGRQLSKRDLYDEEFFRTHFAKQEIESRLEFLLNRVNSLEELITKAKELNLTIDLKQ KNVTFILKENNQKISLGHQKISDKKLYDVKFFQDYFKNKEVIASEGLENLQEQYHAFQEERDKDKVSTEEIEEAFK TFKKPLRHLRKNEIPFVNLKffNLQRTK(SEQ ID NO : 1359)>orf01692MEEENHKKYKVYIRETSSYFVYNKENMDNNCFIKGRTLIRQLSNDSQKLPYRRPTLKSLQEKISEINLM IELSNTNKQYQEIKDELVLEIAEIDMKLEETQEKIATLNKMAEVFINLKSEDEIGRKLAKYDFDQMNMTESIMLDRL NTDILKLQQELGNEINKYEEIARRLDLFVK11NTNKFTVLKFHENALLE (SEQ ID NO : 1350) >orf01693MKSKLGITLRKVRKGKQISLCSVADEHLSKSQISRFERGESEISCIRLINILDKLHITLDEFLVLHNDD YTSSESFANLVQYIRKQYSSQSINNIACLLSDTSDYTLNSFEKTMVKSILHTMDSNIIPSDEELLHLTDYLFKIEKff GYYEIILLGNCVRTINYNSYFLLTKEMLNNYIYSSLNKTNKQIVSQLAINCFILSIDKEEFSNCSYLISKIKTLLDN ELNFYEQTVFLYATGYYEFKRQLSSGIETMKQAIQVLDILGEDKLKLHYTSHFDKLVNNK(SEQ ID NO 1351)>orf01694MSLSYYYEINPSTDILKCIEELLYKEDKCFNNILKNWKDIRRNHNDSFPNFffCYGAPGILLARKEIFDK TNIGNNDLSIIKNVLTNVEKIRELNLCHGSVGTISCLDAILKDEENLLIKESIDFYFDNVVSQVIKPELSTDLNTMN TFSFMLGVSGVVYEISRKQDDRLLNVLLLELRGHDD (SEQ ID NO : 1352)>orf01695 MMTRKVPNIEQMSQIECGLCCCLSILHFYKSKETLLDLRRDIEKGRDGYSIGDLKQL LNKRNFDTGSYQVKDVNKISELPLPLIAFWDNQHYVVIYKVKKNKVYIMDPSKGYINYEFKEFSKHFSNIVLLSFPN ENYQSLKSQFPSPWIRVFSSFSKVKGRLILTLLFSIISYLIILSVPVMTSKFINSALGNTFSFQTSFLILFSLLCLY LISILARSMGILFSNIFFSRDIESFTFKHLLKLPYSFFELRAKGDILYRISSLSGFRELFTNQVVGGVVDIGTILSV VIYMFLSSKTLSIIALILSLINFLFLFSTRKIMYDTVNRELQEQSLIYSVETEALNTISSIKISGLEDEIYENWSKY LKNVLTKYKKRSIVHILYNSATNVFQLFAPIIILIFGLDNVLNGKILLGEVVAFQTMASILFSSEISIFNAYTQYIL AAGYLNRVNDIWLENEENVENGLKKCSLEGRIDIKDLSFSYSKDSAPVIENLNLTIEPGQRIALVGQSGSGKSTLSK ILSGLYKIDTGKILFDGVNINQIDKKILSQNLGVVPQDSFLLNRSILDNITLKNEVTSQKIEEVCKAVQIYDEIMAM PMKFNTIISEMGSNISGGQRQRIALARALINNPSIVILDEATSALDTINEERITKYIQSQGCTQIIIAHRLSTIKDA DIIFVMKGGKIVESGNHKYLMDLGGEYYSLYTKRK(SEQ ID NO : 1353)>orf01696MAIVEIINLTKSFKDIEVIHNTSFYLNKGKVYGFVGPNGAGKTTIIKMILGILKPDSGKITIFNQTVEQ NSENILSRIGLVLGPSFYGHLDAYKNLKLIANMKGLSLDTERLNEYLSMVGLKDVKKKKVKNFSMGMKQRLSIAASL LGSPEILIWDEPINGLDPQGVIEIRSLIRFLQEKKGITFLISSHILSELDKVISDIIIINYGKVEFFGSCHYLLQKY NCRNLEEAYLACLAGGEYD (SEQ ID NO: 1354)>orf01697MIKLEFLKQKKSILWFVLIFPIILNVLLYIDLTFRYRGYLLVHQNELALSNWQLIFKEQTIFYFSELFY LVLSLIIYEVFAVEFKNDAWLTVISLPFRNKYTINSKLLITVVYTFTFWLSDYISLYVIGKAIDNSLEIGLIFFLKT FTIQLISSLMIMLLYFLTLVLIRKISGIIPIGIIMMILTISIYYNDYNFKIYLPFTYLSHAFRVTESQFYMILLSNI 11IVLFYILIRKLNERSFEMKL(SEQ ID NO 1355)[3145]>orf01698MKLLKNELIKSKIFLFIIVDICIQILVILAIKTYILDISALYSELDYNKYWYILHTLIYMLMIFPIQIL YQNLREALIEDNNNGWNIMVINTNNLVKIIYIKVTINIVRCFICYFVYTIFSLIQLGGMGTDMLLTNIIFPNIMSFL LFLPIAIFMQICCIRFDSILAKALPNILLILIVLITFQSDWNIFIPATYYYTEIQSTTNLGIKLLVCIWIMGFEFFL LPKLIKLKEQNLV(SEQ ID NO : 1356)>orf01725MRFSAFKIFSNSVCKRIITKGLGFRALLLYTISKVKLREDILVSQSIVPVEIPQYCRFDSKKRNGILFN VRIANLKFTFFRLDFLRNKIWYSSSMNDEASKQLTDARFKRLVGVQRTTFEEMLAVLKTAYQLKHAKGGRKPKLSLE DLLMATLQYVREYRTYEEIAAVFGIHESNLIRRS(SEQ ID NO : 1357)>orf01753MHTKSRTIKSLITQFTAILLYELPLALDSLVFMGFSMKLIHDLNTHTTHSTAKMLHNVKAIKNDFSIRE (SEQ ID NO 1358)>orf01776MIKIYFTKFSENHNPFCKIFEIIFTNLIFQSILNKNKKNPLRQGEANVV(SEQ ID NO : 1359)>orf01783MSQVKGLCVLDVDGTLILEEVIDLLGREAGHEAEISQITSRAMRGELVFESSLRKRVSLLEGLPILVFD NVFNSIHLSLNVPEFISILQKNGILVGLVSGGFTPIVGEISKIPWYCLFHCQPA(SEQ ID NO 1360)>orf01784MLKSAELGIAFCSKEMLKKEIPHHVDKRDFLEVLPLIDCLE (SEQ ID NO : 1361)>orf01789MFGNWFFKAFVCSLERLAQDRTMNWFSCIGNKNTVAFVPILIGCFA(SEQ ID NO : 1362)>orf01804MEKYFGEKQERFSFRKLSVGLVSATISSLFFMSVLASSSVDAQETAGVHYKYVADSELSSEEKKQLVYD IPTYVENDDETYYLVYKLNSQNQLAELPNTGSKNERQALVAGASLAALGILIFAVSKKKVKNKTVLHLVLVAGMGNG VLVSVHALENHLLLNYNTDYELTSGEKLPIPKEISGYTYIGYIKEGKTTSDFEVSNQEKSAATPTKQQKVDYNVTPN FVDHPSTVQAIQEQTPVSSTKPTEVQVVEKPFSTELINPRKEEKQSSDSQEQLAEHKNLETKKEEKISPKEKTGVNT LNPQDEVLSGQLNKPELLYRDETIETKIDFQEEIQENPDLAEGTVRVKQEGALGKKVEIVRIFSVNNEEVSREIIST STTAPVSRIVEKGTKKAQVIKEQAETGAEHKEVQSGAIVEPAIQPELPAAVLTDKGESAVQPELPEAVVSDKGVPEV QPALPEAVMTDKGDPEQVEPLPEYTGVQAGAIVEPEKVEPEYAGVQAGAIVEPEQVAPLPEYTGVQAGAIVEPEKVE APKEYTGVQAGAIVEPEKVEAPKEYTGVQAGAIVEPEKVEPSKEYTGVQAGAIVEPEQIAPLPEYTGVQAGAIVEPE KVEALKEYTGKIEQPSAEDTKPNNENTNTPEEMSIQKKSSALINMNFITDSSKVTGVGSATFIAPNVLLTVAHNFIN NSTDNTTGEFRGDKSKNVYEWVTPDGQKGTFTANNIHFYNKKDYPKGFIYDLAVIKLPETTGREHVELVKNYSKVNL NDKLNVHGYPAGKYTHLKDATVEMEQEYANNTYGVQYQGGNPGMSGGGIFNANGEVIGVHQNGAQNRSGGLILSPTQ LAWIKSIIAGNEIPPVYDELYRHKDEKKDDAKDEKEVIKKLELRNISSVELYSKDGNKYRHVTSLASLPSNAENYFM KVKSENFKDVMLPVTSITNDTKDNRDVYKIVASANSLIQHENNNVLENYTYYLPKTQQSETGVYTSFKNLVDAMNSN PNGTFRLGATMDAREVELPDGQESYVNNVFHGILVGTNNEKYYAIYNLKKPLFGELNGATVEKLSLKDVNISAKDDT ATLAKEANNNTHIDNVHADGAIAGERSIGGLVSQVNNSTISNSSYTGRITNTYKTVASYQIGGLVGKLSGPRGLIDK SFASIDLSSNATQGDQSIGGIVGAVENSALISNSYAEGNLNNVQRFANVGGVVGNLWDPVGGLEKSGRLSNVLSDVN VTNGNAIAGYNFNGIKANGTYSNKNNKVVNVVQEDDEILTKDSTVQRGEVLEDAQIKEKKATFVSKNTIKTEDFNFSSRYVTDYKNLENADSSKEKVYKNIEKLLPFYNRETIVKYGNLVETSSNLYNKELLSVVPMKDKEVISDINKNKSSIN KLLLYYADNTSETLNVNYQTDFSNVAEYRIGGTNLIYTPNTLLRNYQNILDEVLPALNSVEYKSEAIRKVLDVSKDV SLTELYLEEQFNTTKTNLKDSLTKLLTADAAIAENNNKVIDNYVIEKIKNNKEALLLGLTYLERWYDFKYRDTKAKD LVMYHLDFFGKSNSSALDNVIELGKSGYNNLLAKNNVITYNVLLAKNYKTNNLFDALEKYRKAFVPDKTNNEWFKEQ TKAYIVEEKSTIKEVSDKQSIAGSPYSIGVYDRLTSPSWKYPSMVLPLLTLPEKSVFIIANISTIGFGAYDRYRSKE HPAGTDLNDYVEKKAKEAAVRFRDHYDYWYRILDDKNKEKLYRSVLVYDAFRFGTDEKEDKDTYQATFETNHPAIKH FFGPAGNNVVHNSNGAYATGDAFYYMAYRMLDKDGAVTYTHEMTHNSDREIYLGGYGRRNGLGPEFYAKGLLQAPDH PNDPTVTINSILKYDQSEESTRLQVADPTQRFGSVDDLNKYMHNMFDVIYMLEILEGKAVAKLDTNQKYDLLRKIEN EYKPDPDGNSVYATNVVRRLKPEELTKLTTFNSLIEHDIITRRGYVDEATYKRNGYYTINLFSPIYSALSSKIGTPG DLMGRRIAFELLAAKGYKDGMVPYISNQYEKEAKAQGKVITSYGKQIGLVTDEIVLSKVFNNQYNSWIDFKKDMYKE REDKFGKLNKVSFIDPNGSWARQQKVTIDNINRLEKMIEDAVKFDAEDEVAKLYPETNSRVLKLKKAIFKAYLDQTG DFRSSIFENKK(SEQ ID NO : 1362)>orf01807MTALGLLAIGSLIVIITKDNRNKKIATFLIVGATGLVTLSTASALNLNANIHESGRDGVLQISGYRYVG YLELDDKTVSSVSPASTVSPVEQPKVVTEKGEPEVHEKPDYTQPIGANLVEPEVHEKLAYTEPVGTTGVDENGNLIE PPVNDIPEYTEPVGTTGVDENGNLIEPPVSDIPEYTEPISTVSEVASEREELPSLHTDIRTETIPKTTIEESDPSKF IGDDSVRQVGEDGERQIVTSYEELHGKKISDPVETVTILKEMKPKILVKGTKEKPKEKTAPVLTLDRTNTNVLNRSA TLSYHLVNTDGVTINKITATIKDGNEIVKTVDLTSEQLDKQVEDLKFYKDYKIETTMTYDRGKGEETATLEEKPLRL DLKKVEIKNIASTNLVKVNDDGTETPSDFMTEKPSDEDVKKMYLKITSRDNKVTRLAVDKIEEVTEEGKKLYKITAE AQDLIQHTDPTKVRNKYVHYIEKPVPKVDDVYYNFKELVDAMNADKNGTFKIGADLNATNVPTPNKQYVPGTFKGHL SSVDGKQYTIHNIARPLFDRVENGSVKNINLGNVDINMPWADGIAPVA匪VKNATVEDVKVTGNWANNNIAGIVNK IDSGGQLTNVAFIGNLTGVGDKGQYMAGIAGEIWRGNLAKAYVEADIVANRARIGGLVAKTDNGNDSMGIGKYGSIR KSVTKGTIKTKVLFETGGFINSNLPFGKLEDNISMMRVENGEEFFGSSDLDYDGGYFTNGWLERNFVVKGVSSGKHS YKRSRDKIKEISQDEANKRIANFGLTADKYEINEPVVNRLNRLTRREDEYKSTQDYKSERDLAYRNIEKLQPFYNKE WIVNQGNKLAEDSNLAKKEVLSVTGMKDGQFVTDLSDIDKIMVHYADGTKEEMDVTKNTDSKVQQVREYSVSGLGDV VYTPNMVVKNRDKLIADVKSQLSSVELISQEVRDLMSRRDKPAENTDERKNGYIKDLYLEESFAEVKQNLDKLVKSL VENEDHQLNGDEAAIKSLLKKVETNKAKIMMALTYLNRYYDIKYGDISIKNIMMFKPDFYGKTPSVIDRLINIGSSE KNLK⑶RTQDAYREIIAGNTGKSNLRNFLEY匪RLFTEDKDINDWFIHSAKNVYVSEPKTTNTELKDKRHRVFDGLD NGVHGRMILPLLTLKDAHMFLISTYNTMAYSSFEKYGKHTEEARNEFKTKIDEVAHAQQTYLDFWSRLALPNVRDRL LKSQ匪VPTPVWDNQTYNGSPVGRRGFDSKGNPIAPIRELYGPTWRHHDRDWRMGAMASIFPNPNNDDKVLFMVTDM ISPFGISAFTHETTHVNDRMLYFGGHKHRQGTDVEAYAQGMLQTPDSSTTNGEYGALGINMAYHRPNDGNQWYNPDP DKLKTRDDIDRYMRNYNEAMMLLDHVEADAVLPKIK⑶NSKWFKKIDKEMRSKIQYNDLLGPNQWDSIRDLKDEEKV MTLSSVNDLVDNNFMTKHGNPGNGRYRPEDFTPNSAYVNVNMMAGIYGGNTSQGAPGSLSFKHNAFRMWGYYGYENG FISYVSNKYKAEADKNNHGLLSDKLIINKVSKGNFNTLEEWKRHWYGEVLAKAKKGFEAIDIDGVHISNYDELRPLF DKAVEEDLKKPDDFSHTVALKSKVFKALLKNTDGFFNKLFKEDI (SEQ ID NO : 1364)>orf01818VFHKSLNNCKRKKVCYSSLLPSCFHDWLKNLLTKSQHFSHINFIVEGEGWRSQVRFNHALGNNLTHWC HWNTLDFTIWCYVIRDFFHFFNLSRRFDAIVFDIFRKQGQNILLHDFTTMTGSLDFLPSNVMFEGNSFCKWRNANH VCVFISFHVFFVDTTVCT(SEQ ID NO : 1365)[3165]>orf01822VLGGRANSVTSCTTNSHWNLTFTTKHVTCFSSLVDDIVHGNNREVHEGHIDDWTKSCHGCSCCCSRDGS FRNRTVTDTFWTKFFKHSNRSTEVSSEDTDIFSHQEHIFIATHFLRHSKDNGVTEGHCFCFHFISFSLVCVNIFKG (SEQ ID NO 1366)>orf01823MDMFYIGHFLDIRRDTVTVVNAIENDWQVPDRSHVHCFVENTFIGRTISKEANNDFTGILHLLTEGC TDSDPHTTTYDTIGTKVPSIKVSDMHRSTFPFTGSSVFTKDFSHHSVEVNPFSNSLPVSTVV (SEQ ID NO 1367)>orf01841MISVWHCNTSSCSTCDLRWVENKAIRFHMALTQRQFVELFQETINVITLTCLTVSVAVVACVSICSSWI AYRRYPVCS (SEQ ID NO : 1368)>orf01842MISMRNDISITSILYDIRSIKDITIICSIASLRTCQGNSSIVSWSPSFTILTMFLFLSIDFLFCTDVIR VGSILKVNIVFSIYLDNISTLDLINNILIF (SEQID NO: 1369)>orf01843LVCYLDDDLLSIDSFTLANLIRSQILRFLRRLFSIYIGNTIIFLNRSSLIQSQLVRTNT(SEQ ID NO 1370)>orf01859MDKLIIFIEKGKPFFEKLSRNIYLRAIKDGFISSMPAVLFSSIFILIAAVPNIFGFKWSDEQLAFILKP YNYSMGILALLVAGTTAKSLTDSVNTRSMEKTNQINYMSTFLAAVVGLLILAADPIEGGFANGLLGTRGLLTAFLAA FITVNIYKVCIKNNVTIRLPEEVPPNIAQVFKDVIPFALSVLSIYGLDLIVRNIFGTNVAESVGKILAPLFSATDGY IGLAIVFGAYAFFWFVGIHGPSVVEPLIVAISYANIEANVQLVQAGMHADKILNPVTQTFVVTMGGTGATLVVPFMF MWLCKSKRNRIVGRASVVPTFFGVNEPILFGAPIVLNPIFFIPFVTAPIINVWIMKFFVDVLQMNSFSIILPWTTPA PIGIVMGTALAPLSFVLAITLIIIDTLIYYPFVKVYDHQILEEERKGNSSSELKEKVAANFNTAKADAILEKAGVDA AQNTITEETNVLVLCAGGGTSGLLANALNKAAAEYNVPVKAAAGGYGAHREMLPEFNLVILAPQVASNFEDMKAETD KLGIKLAKTEGAQYIKLTRDGKGALAFVQEQFD (SEQ ID NO : 1371)>orf01861MIFSNQIPLLLSECNPLTNYNHLFSLIISDKRDIVIHWI (SEQ ID NO : 1372)>orf01868MDGFIVTVK11GHLLVVVFSAIPFFKEFCKEVCVCLLSIVTFKVFNFRNQFLVFFRWFVFSMNESFDD ITHKQFTSNLTTKADNVSVQLFFSIKGCCHITNQGRTNTWNFIYSVVDTNTSTTDTYPKISLAASYSFPYFFTKDW VVSPCMVICTKVNDFISF (SEQID NO: 1373)>orf01871MLDFQDRSPWLEGQKEIDLSYDLFSTDAVTLDELQSRTIALRSLKHDKGLKVHFAEFPNLIIWSTLNKG PFITFEPWSGLSTFLEEGDHLEDKKNVCLLEANQVEELGFEIEVL(SEQ ID NO: 1374)>orf01872MKLFKMSCRNIGQAGKILADSGYQGLMKIYPQAQTPRKSSKLKPLTAEDKACNHALSKGEARLRTSLPK (SEQ ID NO 1375)>orf01874[3186]MRRKYKSIALKKELANDSGKKKCHAMKAQAIVTSQGRIVSLDIAVNYLL(SEQ ID NO 1376)>orf01878MKIKEQTRKLAAGYSKHNFEVVDETDEVSNHTYSKATLTWFEEI FEEYKN(SEQ ID NO : 1377)>orf01886LIESQVFSSLQVCCLNLCHLKFQHFDTCLVFLLVFLDFQNLLAHFPIGIKTRLIGFFQVPKSGITKFIQ HLDMQLGTH (SEQ ID NO : 1378)>orf01887MVMLTMNIYKMLPNSSQNRQINHLTIYTADTTTILQDFPTDDNFIT(SEQ ID NO : 1379)>orf01888MTNNICRRTSSQHHIHGINDNRLPCTRFTSQDSHPLFKIEGNSLNNGKVFYRNFK(SEQ ID NO: 1380)>orf01899MPHTRDNWQTRFKNSSYHNFFVKGPEILNRTTSTTNNEQIQIVPLISTRNISSNFLRSPFTLNLGRIKK DVNTWESPADGRDNISNNGSTTAGYYPNSLRKLG(SEQ ID NO: 1381)>orf01900LLEAFLKQAFFCQFFLKLFKLNRKRPNPIRLSFFNDDGVATTWFIDLYTPNHIDLHSFFQVKP (SEQ ID NO 1382)>orf01911MFMSNLCQFFQVWNINQGVTQGFNQDKLGIVFDSCFYFLQIINIDKGCCDTITRKGFFQKIEGSTVNSR SSHYMVTSMGKRQNRISHCSHT (SEQ ID NO : 1383)>orf01912LINVFSHGVDIAIHSATKFIGGHGTTIGGIIVDSGRFDWMASGKFPQFVDEGSSCHNLSYTRDVGAVAF IIAVRVQLLRDTGAALSPFNAFLLLQRLETLSLRVERHVQNAETIVDFLVNHPKVEKVNYPKLADSPYYALAEKYLP KGVGSIFTFHVK⑶EEEARKVIDNLEIFSDLANAADAKSLVVHPATITHGQLSEKDLEAAGVTPNQIHLSIGLENVE DLIEDLRLALEKI(SEQ ID NO : 1384)>orf01913MTRDFKFETLQLHAGQVVTPATKSRAVPIYQTTSFVFDDT (SEQ ID NO : 1385)>orf01917MSQKNNKKKNKRKNLLTNILAGFLILLSLALIFNTQIRNIFIVWNTNKYQVSQVSKEKLEENQDTEGNF DFDSVKAISSEAVLTSQWDAQKLPVIGGIAIPELEMNLPIFKGLDNVNLFYGAGTMKREQVMGEGNYSLASHHIFGV DNANKMLFSPLDNAKNGMKIYLTDKNKVYTYEIREVKRVTPDRVDEVDDRDGVNEITLVTCEDLAATERIIVK⑶LK ETKDYSQTSDEILTAFNQPYKQFY (SEQ ID NO : 1386)>orf01924MRWNIGCHPNRDTSCSINQKVWKTRWQDQGFPFIGIIVINEINCIFVDITKHFQSNLAHTCLGITLSGS TISIHGTKIPMTIYKHVTVAPPLSHTDHGFINRGIPVWVIFTHDIPCNTSRFFMGFVWGHTQFIHSVENATVNRF (SEQ ID NO 1387)>orf01928LKKKWFFVDYYDTTIILLALISVILVLLGFAEMIDLDNPPYSIIDLVIWGVFVIDYSffRFFITKRKffRF ILENIFDLLAILPLNAIFTVFRLGRIFRLAKLTKLLKLTRLLRIIGLTGKLERKISRFLRTNGLIYILYVNIFIVLVGSSILSWEEKSFSDSLWWALVTVTTVGY⑶IVPASIFGKWLAVLLMLVGIGTIGMLTSALTNFFVKDNPDEQIKLD KLQDELSSQRILLEKQSKKIEELHKMIQDLIEKT (SEQ ID NO 1388)>orf01938VVDFKQTRQDPHDITIYSWLRQVKSNTGNGSCCVRSNPFQAGNSFIGIWKLATKVSHNLLGCSLHIANS RIIAQALPSFQ (SEQ ID NO : 1389)>orf01943MAERTVVQVHNAFPEDTTLINSQLIPLVQVVVNQGRKGIVGSCNSMHISSKVEVDVFHWQNLCIPTTSS TTLDPHDWTKRRFADSNHGFLANLVQGIRKTNGKRRLSFTCRCWVDGSNQDQFTDWIALNCTNFIKAEFSLVLSVQL QIWRNTKFLYNINNWLQLNTLCDFNICFHSKFL(SEQ ID NO: 1390)>orf01950LRILDSQPCFFVDFTNDRLRKSLIIFYMTSRKGITRPAIVFRGAILHHHALSFEVFNQTNIG (SEQ ID NO 1391)>orf01957MLFIIGHLNFPTAGSFIDSTLHRLGNRVCIHDDMAFTVTSSTSNSLDESTFVAKETFLVSIENSYEAHF RNVNSFTEQVNSDQDIKDTQAQVTDNLRPFQGLDIRVHVLDLDTHFLEVVGQILCHFLGQSCDKGTLIFFNAGIDFT QEVINLSHSRTDFHLWIQESRWTNDLLNHCLGLFIFIVTRCR (SEQ ID NO : 1392)>orf01958MNVTLKLLPTERTIVQSRRQTETIINQHFFTRTVSIVHALDLPYGHMTLVNHNQEIIWEEVEKRIRRLS FAPSIHVARIIFNPIGIAHLTQHFDIILCPLFQTLGFKQFTFLFKDS(SEQ ID NO: 1393)>orf01959MIHFSQHLTCQSLNFTNTVNFVSKKFYSKGMFISGSWENLYHIPTNAKSSALEINIITFKLNIDQVIQE FITRNL (SEQ ID NO : 1394)>orf01960VAKLVNLVIDRTILLNIGIARRDIGLWLVIIIVGYEILNCIFREKFLKLPIELTSQSFIVGNNQSWFID FRNDLTHSIGLPCSSRPHQNLSFFSPLNVIHQLLDSLGLIS(SEQ ID NO : 1395)>orf01979MNITKTNFLAVNFVFTIPTTIDMAFYSDFLTCILDKSIMIIQSHNYRSIIKRFTTFCSSKDDIRHLAPT ETLDTRLSQGPSQTFCNIRLSRSIGSNDCRHTLVKDDLGLISKRLESLNFDFL (SEQ ID NO: 1396)>orf01981MGFIVCNHLKFACFNLRNHDLIDKFLDLGHILVQKKGTKKGFKGITKNGITIAPTRFFFPLTQLDKLVK LAITRKASQTLLTDNHSTEF (SEQ ID NO: 1397)>orf01989MRITDNQHKIAKEDFVAEYPKLSQALLDRTLDNLSREDNIFIFPNDLTHTPDLDKDQKIFETVNQKIK TGNVIGFLGYGQERLTISSRFSDESNDHFLHYLLNKVLHINLTSLDVALSREERLYQLLMYLFPKYLQAAIRKGLY KEYHRFSHNDSHVKGVI DVRNHLKKNLPFTGNIAYTTREFTYDNPLMQLVRHTIECIKNQKSIGQGVLDNLSTSRE NVSEIVRVTPSYKLADRAKIIRMNKIKLIRHAYFREYRKLQELCLVILSREKHGLGPQAQRVHGILFDVAWLWEEYV YTLLPKGFVHPRNKDKTDGISVFSVGKRKVYPDFYDRERKIVLDAKYKKLELTEKGINREDLFQLISYSYILKAEKA GLVFPSKDKVIDNEIGNLAGYGLFESLRMPHSIVHFVK(SEQ ID NO : 1398)>orf01995[3232]LDEDILLGCILPWKPEAFEKLKAYGNGREELMTDVRGT SCFVIKFGKAGEQLAAKLWEEGKMVYASSAS MTKRLKLAMSKV (SEQ ID NO 1399)>orf02000MAKKIVALV⑶GIGPEIMEAGLEVLEALAEKTGFDYEIDRRPFGGADIDAAGPPLPDETLKASREADAI LLAAIGSPQYDGAAVRPEQGLMALRKELNLYANIRPVKIFDSLKYLSPLKPERISGVDFVWRELTGEIYF⑶HILE ERKARDINDYSYEEVERIIRKAFEIARNRRKIVTSIDKQNVLATSKLWRKVAEEVAQDFPDVTLEHQLVDSAAMLMI TNPAKFDVIVTENLF⑶ILSDESSVLSGTLEVMPSASHSENGPSLYEPIHGSAPDIAGQGIANPTSMILSVAMMLRD SFGRYEDAERIKHAVETSLAAGILTRDIGGQASTKEMTEAIIARL(SEQ ID NO: 1400)>orf02004LANIESHCNFFQSSIFSSLPNTIDSPFNTSCTILDSSKAICHCHSEVIMTVRRTDDLTIRLDILNQVFE DGTIFL (SEQ ID NO : 1401)>orf02011MTAIWEIATSVEFTKTTKFNDHWTATHFTVKSSffFILNLDFFHFFFSLGNFF(SEQ ID NO 1402)>orf02016MPRNRFSFTVRVTREKNFISFFSFFFQVIDKRAFSSDINILRFIIIFNIDGHTGFLQITDMPDTG (SEQ ID NO 1403)>orf02020MKIKAQTRKLATGCSKHCFEVVDKTDEVSSKYCFEVADGS (SEQ ID NO : 1404)>orf02029VHAHTDKLCNGCNRIFNSIISHHTIFRERNKLSHKAIKSTRQEMGPCHVVFIEFFITLHRRLIGNHDNF LTNLVGSGRVRNDGST (SEQ ID NO: 1405)>orf02030VNHCHWKLFIQNLGITFSLIVTLIRMTDSHVVGTDKDMILLVNSLFLIFDIDKLRLS(SEQ ID NO: 1406)>orf02032VGNNDILWSKRTISINGFNDFLNTCIAVSTTLCNDDTFLIKRKIFIYKIFCMRNPVSMNTNYNFFNTWL QDKFFNCMNQNRSIT (SEQ ID NO : 1407)>orf02042LVAPVASSTRFFKNNDSLTSWNNGFIIITINTIISYQRISKGQDLSIIRLVCNGFLVAGHPCIKDDFAC YINICSEGLAFKNCAIF (SEQ ID NO: 1408)>orf02044VVCYFYITIDWSWVHEDCCFFQTIVTFLSQAMLGMVVFF (SEQ ID NO : 1409)>orf02045MAFVLHTEKHHDINLINDFINGYKLSIVCKLLTSPFLRSSEKEFSSQAFQNLHIGFGNA(SEQ ID NO 1410)>orf02046VIQVTCNSNFKTLKVAKFLINGHQIKQALARVLARTISTIDDGSRNRWTSNQFSIVVDLWMANHTDIHS (SEQ ID NO 1411)>orf02047[3257]MCPCRILKEEIGNNRMVFIGKLGSIFKLNSSLDQFHYLIDSEVFHGHHMVQCLLIF(SEQ ID NO: 1412)>orf02059MQEHYTPKGKHLTIDNRRLIERWKNENKSNREIAGLLGKAPQTIHTEVKRGTTLQQVRKGLYKKVYSA DYAQTVYQFNRKRSVKKLILTKEIREKILHYHKQKFSPEMMVNKKQVKVGISTIYYWFHNGHLGLTKADMLYPRKR KGVKKQASPNFKPAGKSIEERPDVINLRLENGHYEIDTVLLTKIKNYCLLVLTDRRSRHQIIRLIPNKTAESVNQ ALTLLLGEHHILSITADNGSEFKRLSEVFPEEHIYYAHAYSSWERGSNENHNRLIRRWLPKGTKKTTPKEVAFIE NWINNYPKKCLDYKSPSEFLLGG (SEQ ID NO : 1413)>orf02076VQFHLIIFQNLFCSLDIVIDSLTTDTELLGNFSKAVIISVVELDIIHLLICQKRRIKFKERIHTIGFFD FHNFYYTKN (SEQ ID NO : 1414)>orf02079MKFNHYFFLFLIIEKQVAIISFFMHFHIIKLVNHFQLLIKLNCISHPNLHIRPSFLSLVLLFYQKEQDF AIMVI (SEQ ID NO : 1415)>orf02085MKKEQFYPLGIFLAAMLGGLVRYLVSTWLPASPDFPWGTLFVNYLGIFCLIYLVKGYLVYKGTSKGLIL ALGTGFCGGLTTFSSLMLDTVKLLDTGRYPSLKPELAFEYRWRPAFSLLFGEEEMVIVYLAIACGLGALVRYFFSRY NQASKLPLGTLIANLLGCFLIGVFYNHVESKEVYAILATGFCGGLTTFSTLNDELQRLLSDKKVFYSYLTLTYIGGL VAIFLGILL(SEQ ID NO: 1416)>orf02097LNRSILDNITLKHEVTSQKIEEVCKAVQIYDEIMAMPMKFNTIISEMGSNISGGQRQRIALARALINN PSIVILDEATSALDTINEERITKYIQSQGCTQIIVAHRLSTIKDADVIFVMKGGKIVESGNHKYLITLGGEYYSLY TKRK (SEQ ID NO : 1417)>orf02100MSLLETAKRHQLNSEKYLSYLLECLPNEETLVNKEVLEAYLPWTKVVQEKCK(SEQ ID NO : 1418)>orf02101LKRPPKQADKSSLGAKGLAYCDQLFSLERDWEALPADERLQKRQEHLQPLMEDFFA(SEQ ID NO: 1419)>orf02102VISIEMRTFFLYSSAFKKHSSPSPINDGLYHLLLQSLYNILELIHDIFQSLKGFILKSTFTNLFPHLFN GVHLWCVWRNKCKANISRNL (SEQ ID NO: 1420)>orf02129METKKIKNLKGQIIVSCQALEGEPLYTPNGGVMPLLAKAAFQAGAKGIRANSVRDISEIKEEVDLPIIG IIKRDYDGFEPFISATMKEIDELVSEGVDILALDCTNRSRPGYDNITDFIHDIKVKYPNQLLMADISTFEEGKVAAE SGVDFVGTTLSGYTPYSPKKDNPDFELVERLVKELDVPVIAEGRISTPEQARKMLDLGAYAVVVGGAITRPKEIAQR FINVIK(SEQ ID NO 1421)>orf02134MTKDILELESQKMSSDTFIDEIKNNYLSIVESTRKLIDGRQIELAIKLIREANQILMIGVGSSGNAARE FESSLLRIGIISKTVIDTHFQLMHTALLKDNDLIIAFSLSGSTKEVEETLLNAKRKNVKIISITNYSSRNIAKLSDCVLLTSKKESYLEGGSLMAKASQLFIIDVICTRLSLINYEDTICKKEEIASLLSNKVE (SEQ ID NO 1422)>orf02135MQIKFIDKVSNLIMLNLLYVASVVTVIAIGSGESALIATLIKIVRHEESYPYRDFANSFFKDYWKNLGA ALISNLPILILLFSLFFLPYIPLPIYIISILRHIGVIYIILHLIATTFLIPLIGRYNNTLKNSLHNSIMLAYKHFFI AVLIRIIEIIPVLLFFILQNQLLVWITLMIFILPSITKYANAFLYNFIFSKYEKLN (SEQ ID NO : 1423)>orf02136MVSGGFRLDFLLETARLARSTYYYQLKQLDGVDKDKEIKTEIQGIDNEHKGNYGYRRIHLELRNRGFVV NHKKVQRLMRILGLTARIRRKRKYSSYQGEIGKKAENLIQRQFEASRPMEKCYTDVTEFAIPNSTQKLYLSPVLDGF NSEIIAYHLSTSPNLEQVKSMLEQAFTEKYYENTILHSDQGWQYQHDSYHRFLESKEIQASMSRKGNSPDNGMMESF FGILKSEMFYGYEKNFRSLENLEQAIVDYIDYYNNKRIKVKLKGLSSVQYRTKSFG (SEQ ID NO: 1424)>orf02137MKLSYEDKVQIYELRKQGQSFKQLSKRFGVDVSGLKYMVKLIDRYGIEIVKKGKNRHYSSKLKQEMMDK ALLEGCSQRSISLDYALPNQGMLS FWPAQYKKNGYTIVEKTRGRPAKMGRKRKKTWEEMTELERLQEENERLRTEV AYLKKLKELEERDEALERERQRQLEKWFQEDFD(SEQ ID NO : 1425)>orf02152MVISKTKKYKGVYKDSKGKIYFQIELGVDPITGKRIQKKGRKNQQGLPFNSFKEAYEEILRLKHEFVNS TINNSFLTFREFMEEIYLKYYQQKVQFVTYQTALPHHQLFIKQFGSKKLSDISTIDCERFRLAIIDKYSSNYAKNMW SRFKACLGYAERLGYIDRVPFKGLDNPRGKHPDTKFWTFDEFKKIINSFDISEYEGLHNYMTIWLYFMTGLRVSEGI ALKWEDIDFERKWIHVHSTIEKDKNGVWYAKQQTKTVAGNRKIDLDDFTITILKKffREVQIKNDDKDYVISRFGAPL CKSTISRIIKRHAKITGVPEITGKGLRHSHASYLINVLHKDTLYVSYRLGHADKSTTLNTYSHWYYS⑶STISEEIT NSLDNLGLSIYLPNSCQS (SEQ ID NO : 1426)>orf02153METVNYKDLVAIGFPEHTSRNIIRQAKKIAVKKFEEARKNDKNAVQLGCSPFDNKRLGIAPKNIVENLI GISFSDIEGEKNGYIKDKEI (SEQ ID NO: 1427)>orf02154MLKRIRDLREDDDLTQEYIAKIVLNCTRSSYSKMEAGSRLISINDLIKLADFYKVSLDYLVGRVDNKED HYSKK (SEQ ID NO : 1428)>orf02155MVITKHFAIHGKNYRSKLVKYILNPSKTKNLALVSDFGMRNYLDFPSYKELVKMYNDNFLSNDGLYEF RHDRQEVNQRRIYSHHIIQSFSPDDHLTPEQINRIGYETVKELTGGRFRFIVATHVDKGHIHNHIILNSIDQNSDK KFLWNYKSERNLRMVSDRLSKIAGAKIIENRYSHRQYEVYRKTNYKYEIKQRVYFLIENSKNFEDFRKKAKALHL IIDFRHKHVTFFMTDSNMKQVVRDDKLNRKQPYNETYFKQKFVQREIINILEFLLPKMK匪NELIQQAEFFDLKI IPKEKHVLFEFNGIKLSEQELGKMNQYSVSYFQDYFNNKNETFVLDNNNLIELYNKEKLIKEKELPTEEVVWKSY QDFKRNRDAVHELEVELNLNQIEAVVDDGIYIKVQFGIRQEGLIFVPNIQINMEEEKVKVFLRETSSYYVYHKDS ADKNRFMKGKTLIRQFTLQHEPQHMYRRIPLSKIKEKIEQLDFLISAENSPNDFEDITNDFIAQISYLENMIEQV QNKIDDLTNLEEVLLNNTTNSSSNLENSIQGKSSVDTIEKDLYIYKGKIETLKEQHGEAINLFEMFNKTIKKYKK KQNMKSIEENEIHLE (SEQ ID NO : 1429)>orf02156MKRDIRSIRKQFRLTETEEKQILDLMREKGEDNFSDFLRKSLLLSDGQKQMEKWFNLWKKQKLEQISRDVHEILIIAKINHQVTQEHVSILLTCIQELIKEVEKTSPLSENFRNKYMR(SEQ ID NO 1430)>orf02157MEYVEAVNQFIERHYKEKDIGHIEIDFWGNKNHPHSLYIYKRSKKIEYDYFFFDSIDYYEEPDFLEFKY IVHLENITYIFWQED (SEQ ID NO 1431)>orf02162MTTLDFKTLFKEEYDKLNKQQKKAVDTVEGPVMVIAGPGTGKTQILSRRVANILTNYHTSSEEIVCLTY TEAGASEMLDRLEKLIGEEGRKVRVSTIHAFCSELILRNSEIFGGQPKIISTAAKYEILKEIMDEYVIEGNPLYKNS GKRYSAKDQLLELFYKMKRENLNKEDFEKEIDEYFKMIDLSIPGDDLYSKFKYARNSKSKDKKVGDYKDKAINELKE NTQKLLAGVEIIEKYSSDISNHNYFDFDDMILWTIEKLEENEGFQRSVSDTIRYLFVDEFQDTSVVQNKLVDLLVKG KDNPNIFW⑶DDQSIYRFQGVSANNIRDFDKKYKPTKIVLDENYRSSQAIIDASRQLISHNPREEKLLIAAGANKD YDYQLPILKSYENAKAEMFGVLTEIKELIDSGVSPNEIGVIYGRNSYGEEFAKILRDKGIFVQMKENKDLFSEPFFK KIVAILKYLCKPSRDVRELRKIVYFDFFEVVLSQIVMIRNLKKDEKISIPTIAEIDQKLEIIRKKVNQSSKYLSPMY VLSDVLKSLSIDEYIMKSKEKYHLVSVLNELYKLMLMECHIHPKLTVKGFLNQLSALEEMGISLPIEDISGSPSNCV QLMTAHGSKGLEFDHVFIMKCNDGKKKSEAWPGGENNSGRFSYPPSLNGKDENESQLKEEENRRLFYVAMTRAKKVL HLSYANDSTKTHLINEFEEFIDEVDVTESFEDCQSVDKVVMPKFSNNVINEIFDELSLSVSTLNSFLKCPLSFYFNK GLKLPSETNEAMVFGSIIHEVLEKIYISVDGSQSSELTAKTVLSLEEALKLFETVFEEKSYQLTSNKIKKDDYARGK KIIENLYKKSGYLKDGVVAVEVPIQGIRL⑶ILNTTVDLSEVSNIEINGKIDKIECDGNIVCLVDYKTGNFENAKKK LVAPSEKEPLG⑶YWRQAVFYYILFKNAGIDISDKEILVKYVLVENSTNEDGFSETEDIRITQKEVDIVLNQIKESI MKIKQGDFNCGCGVLKKDRDNYPCDYCLQVSANTTPKFDNTEALEVATYQQTRGNYKSLSVSKLNRYLRCPKSIYFE DVLQLSQAAGLSAGAKEKSTKITINHAPTGPVFGTAIHETMEKIYKEDLQLEDAIEFYDSSLYSHQEEIIDTMSVEE LKEYGHNLLTNLFEHFIPNSLKGEHVSLEKELRVKL⑶NYSINGIIDKLEFDNDLIRWDYKTGSAQRGVEELEVGH DYWRQAVFYNLLLENSSEIDTTDKRIETQYIFLDDNSTESGYSIHTIQVTKEDLDLVTSQIQNFWSHMNTADFTGSC GKNDCDYCRLAEFVDFELLKETIESGKESNLVN (SEQ ID NO :1432)>orf02163MSGRLTRQNYYLLGKLIDEFHAVKAAMRVIETKRNDFNI (SEQ ID NO : 1433)>orf02164MKPQERLLTIFFRLQAGERLSKAQLSDEYEIDYRTVQRYMSTLKNFLQEQRISNTEIKFDTSDNTYRL IAKTTFNKKDILVISKILLENRALNKSELYSLLEDLLSLLSSEEQKEIDAIIGSERFNYKSLTNDKDRIDTIWILS EAIRREQMLEIEYKAPLKDIKSHIIFPVSLYYDAHYFYLVAYHLKHENYTTYRVDRMESLSESHVKKPEISYGRK YRDGEVRNQKVDAFEGRKIDVTLIYKGNTEIVLDQFPEREILSENHDEIKVKIKTQDTPGLKRWILGQGDAVTLL SPSKLIEEIQESLENTLRNYKK (SEQ ID NO: 1434)>orf02165MSVQKTKNTLNEPLKTLLDEYHDKVGKINNSSELFDIYSPWNNFNIEKMIESFNKALQSNSNNFSWLD IEEDLPKSTDVDIKYGLPNHIKGNIDEATLFLCLVNPNIDEVKTEKKDVGIHTYYKKAREMES⑶DSLNILNDKGK LRIDPKVYIKEHILDVRETSSILYNELQIVKQTRSYKDTYYLGHYLPHFIKEFLNKKGSFKNVIHNLTDEWDELEK MSKKIANLEAFPFRSQNPNYTYKSNKRATNFTNLLIESDSKVNLLSARVIIWRIVKHLESSQHKPAFILRRFNTFff LPTISKVLEQDLNFTKEEINQIINALDEEYFFTVRKKDYNGQSGYFGRNFCKNNERISNSSFKHLVQETLGEYVKK (SEQ ID NO 1435)>orf02166[3305]MSGSFSDSPTHDDKFSIENYINGLSNFIIECETPLTVAIQGDWGTGKTSIMYQVEKRLNPEKQDKKIQT IFFNTWQYSQFDMGNNLAVALITDLISELNVEDSKKKQFFKKAKGALSKGLEYVNLDFGILNGEKLTEKFQDLIIGF GERTDDIKHLKENLQDIINDAIKENKSDRIVIFIDDLDRLVPEKAIELLEVLKLFLDCEHCVFVLAIDYNVVVRGAK SKYGKDLDDEKGKAFFEKIIQVPFTVPVANYDLQNFIESSLKKLDFCFDKNNKERNQLETITQLIRYSIGNNPRSI NRLFNSVSLLMYINNGDKVDHDEKLMILAMVCFQLRFEEAYNYLLTAYNNSPEDSDDIESYLIDLLENSFELLDDE VYYNSLVSLLGKFTFKDKKDRDDFTNFYRTLKELLGYNEQGLTMEQFNKLIEKMTFSNAVSIGNTDTITADKKKQNH APNEDVQFVIRKLFNTLVGDENYFDLKKPELFGKETREKREAPLSEEFISIPNEFDRIRLTRGKGQGLNIYSSHNK SNFIYISGDTHGRMLNDGMAIVVNNNLVEKIKDNILASDLRSEELYHEFEMNFRDNLNKLLSKASKILNN(SEQ ID NO 1436)>orf02167MEFIRAANQFIENYYPREDLDRIESIEIGIRDSENYSRYFLEIQKQSEEFECDFFNFDNIDYYVVDDSV HFKQIINLENSSYVFWKDY (SEQ ID NO: 1437)>orf02168MNKPIAAIFDIDGTIFRDSLLLKHMEKCVSYDVFPNSVNSEIKFHKNAWENRELDYDDYLYIAATLYTK YIADKDILDIDFVAKKVIEKESKKLYRYTRDRIKWHKEQGHQIIFISGSPDFLVSKMAEKLGADIWYASNYLQLDSK YTGEVIPMWDSTSKLQVLKKLFIDFEKSYAYGDTTGDFTMLQSVGFPTAINPNKKLLDKITMEKLDCKIIIERKDVI YKLDEVTHGIY(SEQ ID NO : 1438)>orf02169 MTNAKEFALTAHKNQTRKGKITPYSFHLFLVNNILETLTEDPHIIATGWLHDTVEDTDVSLEDIKQEFN DEIYSYMSLESEDKSIKDWQTRKELQLAKFREAAEDESLRKVLLVTFSDKLANLMELYQDYLIIGGLLWDRFNSKDP KKQRWYFNEFYKIFKDNQDLFSKNKDILNNYKEILKLLFYNN (SEQ ID NO: 1439)>orf02170LKAIVKNPKRLFELLRLYFVPVKGRKVVHVPAYAYKEDENEKIYLHNNELHLSKKMFEFLVNQGLDLVE CLPEE (SEQ ID NO : 1440)>orf02172MANSSEAHGRVYIKASNLKTIEDFLLIQEERNKYVYYPTDIIDSQSNISDIVSSRTTQENGYYICNMWF TAEGRWCFENNIDDFFDCTLFQDTDDVLIRQMKEYVCSQDIQIKFEYVDAEASQNFVKEQEATITYNSKTKDISIDV KTIKDLPYTAENLIVYGYYECDEIVSVQFLLDYYDDYLRGNEFYLKHKDGIVPILERQQ (SEQ ID NO : 1441)>orf02173MAESALINLINFSKENEELTNLVSGHASKREKATISKDGLIQARSIENFIDNYALSDFDFSTIKEKCVF IKINNSFQADDTTEDIYHNVRGVWNISESRKKDLEYALALYRGVCVGVYKIQGWKKAYEHSSEYPFPTRKEGGKIET SEETIVKYSNIEDLKKDYPELYKRSFSNSEFPQKSLDKWRNRSFFYGNWDGSDVPQHLAQCLNKRIINIPKFTKSVK EFKSIDNQASVIYNDLK(SEQ ID NO : 1442)>orf02174MDLVEDCNTFLSFVADKTLEKQKLYKANSCKNRFCPVCAWRKARKDALGLSLMMQYIKQQEKKEFIFLT LTTPNVMSDELENEIKRYNNSFRKLIKRKKVGSVIKGYVRKLEITYNKKRDDYNPHFHVLIAVNKSYFTDKRYYISQ QEWLDLWRDVTGISEITQVQVQKIRQNNNKELYEMAKYSGKDSDYLINQKVFDAFYKSLKGKQVLVYSGLFKEAKKK LKNGDLDYLKEIDPTEYIYQIFYIWKQKEYLASELYDLTEQEKREINHKMIDEIEEEQ (SEQ ID NO : 1443)>orf02175
195[3321]MNFNKIDLDNWKRKEIFNHYLNQQTTFSITTEIDISVLYRNIKQEGYKFYPAFIFLVTRVINSNTAFRT GYNSDGELGYWDKLEPLYTIFDGVSKTFSGIWTPVKNDFKEFYDLYLSDVEKYNGSGKLFPKTPIPENAFSLSIIPW TSFTGFNLNINNNSNYLLPIITAGKFINKGNSIYLPLSLQVHHSVCDGYHAGLFMNSIQELSDRPNDWLL (SEQ ID NO 1444)>orf02176MNYQKLNDITGATKNEKDKYYVYGLYEEGKQLPFYIGKGEGTRLISHIDEALTEINQEENIQISKKIQI IRKHKGKIIPVII (SEQ ID NO : 1445)>orf02177MTTTKNPWNQLSNVDINGEQAILATEDVELIKKYTSTKHYKNLKDDIYRLQLGFCPQQFV⑶IQNADII VLSKNPGYTPEFKTLYDHDKNYQKTLLNNLQLKGNLYFHAFDLDTNEFGYWAKKFKVWFDDVDNLQDLKEKLPWFSK HVALAEYFPYYSTKYDDKLNDFISKEGYFPTQKFLFNLIRERVLDDNDPVIIIITRSYNKWYDAIPQLKEYKNCYET SNPSNPSLKPENLLKVKRYSAKKEVEKVLEDSLKKLEHK (SEQ ID NO : 1446)>orf02181MFTKLFKKNQDNSDVFKKLIHRLSDMSIQDLKKIDRLLDIIFTPDQGSEQLKTEATYREETLDDTLKEA KNQLHMEQLEKNLERFRKNSQ (SEQ ID NO: 1447)>orf02183MTKDWNFNQPLESKSENQEDPDKIAALFGNHQGGNEVNYEAAFQKRKQAPVTESNSSSKPKVTEVRTGK ETDITTSYQQHLKRLIADNNSDIQSSQKKIEELHTLIDTKNKDNKKLQSIYDAISELH (SEQ ID NO: 1448)>orf02185 MT11ERLEEKVTRQESKVARETEKLAAYKEQLETAMFATFKRRQSISHMSFEEALDHAFGKERQFDDSE FRKDEMSE (SEQ ID NO : 1449)>orf02187MEIEECKKISILDVANRLGISFKQVSSSVYEHPEHDSFRIFSTTNTFKWFSRDIQGDVIDFVRLVKGI SFKEALAFLSEEPFQKEAVQEKRERPFYYPLKRIEDSNCSLARYYLTECRGISEEIIQKMIQQGLMSQASWKTNET VEPVIVFKSFDHRHKLQAASLQGIYKNHSLPRERLKTILKGSHGHVGISFDIGKPNRLVFCESFIDLMSYYELHQQN LFDVRLVSMEGLKRSWAYQTLRLIAEENQKLEFLDTVIPSKLLPLINTIRDTTSYFDNHPDLLTLAVDCDDAGKDF SDKLSRSGFPVFLDLPDNESGKEKRDWNDILREKKSDLQLMIENAKETLRNQPVRQTSQCLEL (SEQ ID NO 1450)>orf02189MLNKVKTKALISVGAVAATSFILMVGYTIGQHSTAKQSRKEIELAATKLVEDKQAEDKASILSSDTVKE FLTQYYTKEKLGENNTRIQPYMTESAYSQELSSQNDAMNQVYKDYILDYHFEKADIFVNQTTNQAIAMVSYNVTYVS DLKNANQSKTNQTETRTVKLSYSKLPGKLLVNQVQVWKSGLDDLDKVTPKTLEESSSIPSLPNTTTK (SEQ ID NO 1451)>orf02190LKKVKFIQQLSETSCGLACMAMILDYYGHEANLYELCCDFENSRDGLSIREIKDIASYFGLDSKATEIL NIKKFLGNKFVEPYIALTQNAHYIVVEKHNEHSVVFIDPERGRITEDISNFANNISGIVIFFSPNRKFTKKKKHSNF FKILKIGKIDIKRLCYISLISILVQSLTLLLPLLTRFIIDNVISKGEMYRLGMLFSIFSLITFYALFSFIRTKLIIT VEKRYIFTLKDKIVGKIFTLPMKFFDSRSSGEIVTRINNLDSLEKIISSGISSLLIDLSTIIIAFIAMAMISLYFTL IITCFAIFLFIVLYFLLKKLEEKNSNFISSKELTQGYLMEIFSNLLFLKVSAKGDVSYTKWKEMFSNELKFDVERENYLNIFQTFISIYRLVPNLLILILGGLEVQQHMMSLGSLMSFLSLVSLLLSPITLIVQNCFQFQFCFTILDRVFDIIY TPEEKNQFSISKLPPFEMMTFRNLSFAYSSACKVIYDISLTIKKGERIAIVGRTGCGKTTLIKLLLRLYDVEKNTIL YNGNDINLFDLNSYRKSFGVVLQNDVMFNDTVISNIDLTHSHSMEDVISAASLAELDIEINNMPMGYYTSIGDNGNN LSGGQRQRLAIARAILQNPEIIIFDEGTGQLDTITEKKIMDNLKHKGITQIFITHRLSNAQEYDNIIVMDNGKIIDS GKHDELCGKEGMYKRLFETSYN(SEQ ID NO: 1452)>orf02191MNRKLNITDFKDASYFSERKISSHDL⑶GLKSRKRKEYWDNFIGEGSNEFWKYLQEKNDFSKHDLDIFL EEHTYDVKDIDSFSHMDEFIEFFFKRNDYTLPEFYIVDSEGKRKPIFSNFVIPFLKFAAYKLEDNLSSQNLKVTRDV LNSLLIALFQQILNISYRTLILELQVLKEQ匪LKGETGEKRFKYFSEIYLSDHFWDILKEYPVMFRLIIENIQNWVT NNVEFLTNLKEDKALLQEHFSINGELTKIESGVSDFHNHGKSVYLLWFGTNKLVYKPRDLILDVKFQNLLSWYNLKF NKNLYVTNILNRGNYGWVEYIEHLPCTYESDFIQFYTHLGYLLFLLFAMRGNDIHFENIIAKGNRPVLVDIETLFHN TTEYRKEYETADKLIFSLLEKSVKRVGILPNIVWGKDGNSGVDISGLSSSAGEMIPIERASIMHSMTDEMKIGYEQS ALQSKDNQPFIQSGKDVDLNSYKNYVSAGFKEAYEIISKDPSSIEEFLVEIEKFNNAYSRQIMRPTQFYSNLIQTSY HPSFLRSGLDREMLFSKVWKIVFEDKKVQRIASSEFESLLL⑶IPLFQTKISDRFLCSELTKYQNFFNISGMELAIQ QIKDFCQKDMEFQLNLIETTLNYDPSYNLVQDSFVPLKPSVKVIRNLNQKEIQETKSRIVPLTEKIADYLSKISYSG TS⑶ICWVDMNILGEKTNDWNMVPIGCDLYNGISGIMLFYLFLYLETKKKDYLIYLKKCYRSLKYYLDSRKQFATHS QVLFGGFSGETPIIYVLLLLKTRMPEHFNSDELDVYIYDIIDDLKKGYRYDENFDVLVGSAGAIIHLLNVFEVTRDE ELLILAHDLFSHLEKNSTKITVEGQDGRAWKGTMASNPLAGFAHGVSGIVWALSKLSRYFPEDKKLKTIIKQGIIFE NSMFDTEKSNWSDYRETESGIKYKDIVENIPVSWCHGAPGILISRLELYKNNTLNVEFRRTMKSDMDVAIDTTIKYG FGKSHCLCHGDLGNLNILFYVAKKMSSEHLYNVVYSYLNTILDDLESENWKCGLPYKNSPSLMSGIAGIGLGLLTLN NLSIPSVINLEIff (SEQ ID NO: 1453)>orf02192MLMLEFTKLRRRKILYMIPFVAILLFLLEFMIGHQIYQGHSYGSVNGWYVENGFFFLNYYFLLPFASMI LVDLIRIEQVSKTISNLRLIPVDLKQLLQAKFMLALLINLLVSEFTFLAMLVLELMD⑶FAFSSLAMLSWGWYGAI AFAYTLSAGIIVLFLGKYRKELILALPLAFLLSFAGLFALTTVVGRYYLANLLLIIMEQFTALTVSVYAIWLVTLVA CLLYLLADKRMMNIIFAYK (SEQ ID NO: 1454)>orf02194LLDLVKIEFLKQRHQKLNFVVYGVVSLYLALICYYVNDARGLFDSFPFVYKFSLSYLNFLILPLYCVSY TIQAFGLEYRYRIMNNLKLASANLMKTFWAKILYIEINALCIMLFTYISVSLFALLSRFSSTVSLSLLLRFFYLCMS SGILIPMGVFPLVALVMIKVRGKEIVGNLVGVMYVLVSFFLARTSPNISPVTSANSLIWEGNREGVVLQQPAILSIV VLGLSLLVLSFLSIKSWLRKVDE (SEQ ID NO: 1455)>orf02195MRNPVIQTFNLSKSYDGKIVLDRIDFTLRQGEIYGLLGRNGTGKTTFIKAILGLTAMDSGEVNILSEK LLGEFSKDLLSQIGWLDSASFYPNLTGPENLSIFARLRGISLKQVEQALQVVGLDGENKKLFKQYSLGMKQRLAI ANAMHQPKILILDEPTNGLDPIGILEMRRYLKELSTNHGISILISSHIISELEKLVDRVGILHDAHLMAEKTMK ELIDGADKRKIHLIVSDAPQAKEVLCRINLQEQISILSDIELELQGESPTFDIAVVSNSLKDNGIVLKEYSYKNN ESLEDYFKRITGGEGIA (SEQ ID NO: 1456)>orf02196MTILSDKLKAKRKEKGFSQKTLSEGICEQSQISKIERGNYMPAADLLYKLANRLQVPLDYFFDEQIEM
197TSNITPFKKLAEKLLEDRNYEDLEYLLNLEKEKSQYLSTEDEFYLLWIQSIILFYLHSSKDEAIASLENALPKLSV SSSVYLKLLNTLSNFYFSVGRDAEYEENNSLLISLYQEKDLNHQEYLFGYIRVKHNFAYYLHSKGKELEAVQEALE TIDFCKQKETSYQLAPLLTIVANAGKDFLKHDEILDYYLQARDICKIYEHKLMMAKIDHFLKDKDR(SEQ ID NO 1457)>orf02197MNDLLLIPVIFLAVGGILILLWRLFLIASGLFLIGFVSFLIFVEVYGIYLLFTETELYTADLAQNGLFG FTTFFIIFNLVLLALACWAGYKWKRGY (SEQ ID NO: 1458)>orf02199MEDTYYQLEEALVQGFQTPEEYQAYKELKEHYEEVTGDYSFSKRELTSQLEIALQNHRGVDFEEYEKKD YLELVQKLEEFDSSLATHYRQLID (SEQ ID NO: 1459)>orf02200MVRRWVLSLQRNGRIIRQGNENKEVDIYHYITKGSFDNYLWATQENKLRYIKQIMTSKEPIRAAEDID EQTMTASDFKALATGNPYLKYKMELENDLTLLENQRRAFQRSKDHYRHTISYCEENMPILEKRLSKYE⑶IQQSEI SKDQAFSMRVGKQSFDQRAEAGESLHRLIRHNQADSKEFRTLASYRGFDIKMLSLPTNQPLPETFSVKIVGENQY SVSLDLYSPLGTIQRLQHTIDHIKEDQVKTQNLLDELKDKWNTAKVEIEKNFPKEEDYQTKKAEYDVLAPLIETE TDLDTIDQALRQFHEKGKEKQEQLSFELD (SEQ ID NO: 1460)>orf02202MRNPQNVLNNLTKHSKDKNYQFERLYRLLYNKEMYLVAYQTIYANPGHLTPGVDELTIDGMSIARIDQL IDSLKDESYQPHPSRRTYIPKKNGKLRPLGIPSFDDKLLQQVIKMILEAIYEGQFEPSSHGFRPNKSCHTALTQIQK TYTGTKWFIE⑶IKSFFDNINHDVMIHILRERITDERFLRLIRKFLNAGYVEDWKFYKTYSGTPQGGIISPILANIY LDKFDKYMTDYVKNFCQGKYRKRTPEYRQNEIALGKARRALECVSTENQRQEVIQRIRQLEKERVLIPHSDPMDSSF KRLTYTRYADDFICGVIGSKEDAHRIKADIKDYLEAVLKLELSVEKTLITNARDKAKFLGYHLYIRQSNLAKRDSAG RLVRNYTGRLVLEVSIETIRDRLLSYGAMKMTYHRGYEVWKPTARYFMKDCDDLEILERYNAEIRGFYNYYCIANNS SILHRFKYIMEYSMYKTYATKYRTTKSHIIRKYKKDGQFSVQYIGRKGDTMTRYLYNGGFKRQKKSFLENDNLPNTA KYFSRTNLIDRLKASRCEYCQATDSSLEIHHVRKLKDLKGKTFWERLMISRQRKTIALCKDCHKKLHHGKLD(SEQ ID NO 1461)>orf02208MEVMKLLAMFRGTIPKDREKMDLFLRYQAQHFDEKWQDLVESFLAEEGKIEEIPHVYSFHQDIISFLEA SSENNDQDLESYTRNFGQAGLSKLSQLSNFEKNLVLEVATYNLSTRFYIQSEKEKLEPLSELVCLQNQDVNLVNVYR VANNLSDRISRDIEEFLLMVDSKELTKEVLEIHFEEKEGDVLAYLGSELMATLDTVTDLVHHEENYTQLPLTQKLKI ITHFDDVKARSEKSNQVEEVLSPSSDIEQETEETNSFSNVDKIVEEALREYPIGSQVSYKGQVFQLVSIENAQLNDL IRLELFNDSNQLFEENPILYLNSLEEIEQVLSLVELEKEDSEIEIDSSSESQEIDLFSYLEEEKENEKDKETETLIV GIEETDVPVQDFVFPDDLEDFYPKTNREKIETNIAAIELVKRLEKEGRQANPEEQELLAKYVGWGGLANEFFDELNP KYETERLTLKSLVSKSEYSTMKQSSLTAYYTDPMIIRQIWQKLLDDGFEGGRILDPSMGTGNFFAAMPRSIRDKSEL YGVELDSVTGAIAKKLHPNTHIEVRGFEEVPYQNNSFDLVLTNVPFGNFRIADKNYDKPYMIHDYFVKHSLDLVRDG GQVSIISSIGTMDKRTDNVLQEIKTNTHFLGGVRLPDTAFKSIAGTRVTTDILFFQKDQAKNLNEEELVFSGSIPFE EDKRVWINPYFDGKYNTQVLGEYEVRNFNGGTLNVKGVSETLSTDIMKALENVEAPKQIDNFLKAPVFIQEEVDNSL PSRIREDLALYSFGYERNQIYYRDTHGIRKSSKVDEISYYVDEKGDFKAWDSSLSEHKIDRFVQLHLTDEEALDVYK SEEASKRGKYKGLFKKTVFYESPLSDKDISRIKGMVDLRETYQSLIEIQRHQDYSRTDFQVLLSKLNHNYDRFVSQFGYLNASVNRNLFDSDDKYSLLASLEDEYIDSKDQKVKYKKSLAFEKALVRPERVIARVSTALDALNSSLSDGRGVDL DYMVSIYPEHSQAAILDELGDQILIDPESYLRGERKYLSKNQFLS⑶ILNKIEVVQLLVEENNQEYDWNHALDLLES VRPPRIHLADIEFKIGSRWIPQSVYGKFAFECFTNREFELSSPDVEQVIEANPVDGQVHLRTSFAYRYPSAKDSSLG VSGSRYDTGRKIFENLLNSNQPTITMTVTEGEKKKTITDLEKTSVLRAKEQHLQELFQDFVSRYPEVQQVIEESYNR LYNRTVSREYDGSHLVIDGLAQNISLRPHQENAIQRIVEEKRALLAHEVGSGKTLTMLGAGFKLKELGMVHKPLYVV PSSLSAQFGQEMKFFPTKKVFVTTKKDFVKARRKQFVSRIITCDYDAIVI⑶SQFEKIPVSKERQMNYIEDKLNEL REIKTHSENKYTVKEAEQSISGLEKQLEELQRFNRDSFIDFENLGIDFLFVDEAHHFKNIRPITGLGNVAGITNTTS KKNVDMEMKVRQIQEEHDFKNIVFATGTPVSNSISELYTMMNYIQPDILKRYQVDYFDSWVGAFGEIQNSMELAPTG DKYQPKKRFKKFVNLPELMKIYKETADIQTQDMLDLPVPEAHIIPIESELTENQKLYLEELVMRSDMVKCGTVDPSQ DNMLKITGEARKLAIDMRLLDSSYSLADNHKLLQVVDNVERIYREGMENKATQMIFSDIGTPKKKDNGFDVYSEIKA LLVDRGIPSKEIAFVHDANSDEKKNSLSRKVNAGEVRILLASTEKGGTGLNVQSKMKAVHHLDVPWRPSDIQRASVK AV (SEQ ID NO 1462)>orf02209MEGIYQRDSDQDGLTDAQELALGTNPLSADSD⑶GRSDLVEVEEGTNPLEKDLQDIDQTSITEPSSVFM EMKQKISDMMESHYKEFIQALISIETGIENEQDLEDLYTYYMRTDSISLLSSDLETSPQKVEMEIEL (SEQ ID NO 1463)>orf02210VADTRTKSDSNLGRKGQAVADTRINRLTRWLTDSVNHLFCEENMANSRDYRNPNYTEKIKLQRFFTQLQ IAASFFKEHFVGKIMYYETEIESVELHFSPTNFMHLCGVDYRKGAGSFFDDCLNRHVIIDELKIKKDGTTMQKLQVL GSIEELLGKHVHLTGSGRYLYLEFDYALRTRKQILALTLKETSRKIVPQSLLDLKRKTVFPKGQKVISIYSKHLQTS ELFYYLKD(SEQ ID NO: 1464)>orf02217MKDKREIIRARKAFRRSLKDEKKFLKKGKKEVKKQKKDSAVLDEKAWKKEIKKKLEEMREASKARVKQA NEDYNHILQNSPPSLLNRKELRDRRLPHARKRLKIAKKQYREAKVEAKEERKESRKERKTNQKFLYGQESKAKSNFF FQGKSLEELKVKKEVKTAKENLKSTKQAYKSKKVSRKAKTFLYVLGREGGELASENEDLDGYRTLQETIRKGKRYSR LSYNLGKASVKTGQATCRFTKKRLTNTKERYHHFKDGKGWKLAKDKPSSFKNRFRKLKKQGLTSVRNIYQKLKAAFS FFTFAAGNPVTWIVGGIVFLLLLIMSFFLGFSSASLIQQDEFELTKAYTHLTWEDAEHTRTNDKGITYYTKVDDVMG YMNFKFHDYELHKPVHLFSSETYKDYLSTLWHDLNDGEDLKSMQDLYETPKYKLSKDDQEEMKELKEEGIYASMQEL DNPFEGKSNEDSLTMTYRYGYYDLDGKPTLQEYILLEAKAHQTIVAPMDGVVSLD⑶NVILTNGKGENESRLTLYSI HNGRAIEGTRVLTGDIIGETPDDTGLKVSYQKYKNKKEKLVYVNPQFYFPKVIQLQTTILPAIGQFGGDEFERAKHI YEFLKSQGASPQAIAAILGNWSVESSINPKRAE⑶YLSPPVGATDSSWDNETWLAIGGPAIYSGAYPNILHRGLGLG QWTDTADGSTRHTALLNYAHSKNKKWYDLDLQLDFMLHGDSPYYQSWLKDFFGNTGSAANLAQLFLTYWEGNS⑶KL LERQTRATEWYYQIEKGFSQTNGGQAKSDPQSLEGVRGDLYDHSVPGG⑶GMAYAYGQCTWGVAARMNQLGLKLKGR NGEKISIINTMGNGQDWVATASSLGGETGSTPKAGAIVSFVGGTHGTPAIYGHVAFVEKVYDDGSFLVSETNYGGNP NYTFRKISQADSAISFAYTTK(SEQ ID NO: 1465)>orf02219MTYKKEEVKGKKEEVLPSTANTISYQALYQNGLMQVKEDYFSQSYLLGDVNYQTVGLEDKGAIIEKYS DLINSLDDQTNFQLTIFNKRLNLEKFRQSVLYEEKEDGYDTYRKELNRMMNQNLDSGENNFSAVKLISFGRKDSNP KQAYRSLSQIGEYFKSGFSEIDARFESLAGEERVNLLADMLRGEHHLPFSYCDLTRSGQTTRHFIAPNLLDFKNKNYLQINDRLLQIVYVRDYGMELGDQFIRDLMQGDLELIVSLHAQSSTKADAMKKLRTKKTLMESQKIGEQQKLAR TGIYLEKVGHVLESNIDEAEELLKTMTETCDKLFQTVFLIGVFGQDEEELKQALDTIQQVAGSNDLMIDKLPYMQ EAAFNCLLPFGCDFLEGVSRSLLTSNIAVNSPWTSVDLQDRSGKYYGINQISSNIITIDRSLLNTPSGLILGTSG AGKGMATKHE11TTKIKE SGENTE111VDPEAEYSVIGRAFGGEMIDIAPDSQTYLNVLDLSEENMDEDPVKVKS EFLLSFIGKLLDRKMDGREKSIIDRVTRLTYQSFKEPSLEEWVFVLSQQPEEEAQNLALDMELYVEGSLDIFSHK TNIQTGSNFLIYNVKKL⑶ELKQIALMVVFDQIWNRWRNQKLGKKTWIYFDEMQLLLLDKYASDFFFKLWSRVR KYGASPTGITQNVETLLLDPNGRRIIANSEFMILLKQAKNDREELVQLLGLSKELEKYLVNPEKGAGLIKAGSVV VPFKNKIPKGTQLFDIMSTDPDKMASN(SEQ ID NO: 1466)>orf02220MNTRVFKDISKYQHRAWLGFTTRQIIFVLPAFIVTIIVLGLNLFFWQF⑶WFVYGFVFAFTIPLMLFGV YKPNDLYFEHYLKYRLHFELTVPLRTITGKKGHEHEKKIKYIKETKSFNDL(SEQ ID NO 1467)>orf02221MNLSLVSPFVYLASEKISAENLFEGFSVDLQSTVDLIKSLSSYNPTVWTYMSSITKSVMQPLGVAILSV VLILEFSKMAKKIANSGGAMTFEALAPMLISYIMVAVVITNTTVIVEAIIGIASHAIEQVASIVAHGGAKYDTISGL KGSGFIGRMIVGFFALLIWLVRIVSAAMVNLLVSIRFIQLYLMIPFAPLTIPTFLSDEWKSIGIGYLKNIMVYAVQG VLIFLIVSLVPLFESAGKIAVSNGAGVLQSLAIMFGSLVQAILLIIALVGSQRTARSILGM(SEQ ID NO 1468)>orf02223MITHFKGFVYGVDASAMFAQAMSLLQKGLIAVGAFLVVVGIVNLATNIKDGGPGVRNAILEIVGGVMVG AAGAFVTQISI (SEQ ID NO : 1469)>orf02224MMYSGKKFLLFSLLGILLGYLFHRLTLLYDSYTGNSLDKWTHLLMEGQDEVLQSPWNVSFTGKSSAFFL LGFVMMLLVYLYLETGKKQYREGIEYGSAHFGTLKEKKLFYGKEFSHDTILAQDVRLTLLDKKPPQYDRNKNIAVIG GSGSGKTFRFVKPNLIQMNSSNIVVDPKDHLAEKTGKLFLEHGYQVKVLDLVNMKNSDGFNPFRYIETENDLNRMLT VYFNNTKGSGSRSDPFWDEASMTLVRALASYLVDFYNPPKTREQLIEESRLSQKEHQNLLKRQKKEVEERKKRGRYP SFAEISKLIKHLSKGENQEKSVLEILFENYAKKYGTENFTMRNWADFQNYKDKTLDSVIAVTTAKFALFNIQSVMDL TKRDTLDMKTWGKEKSMVYLVIPDNDSTFRFLSALFFSTVFQTLTRQADIDFKGQLPLHVRVYLDEFANIGEIPDFA EQTSTVRSR匪SLVPILQNIAQLQGLYKEKEAWKTILGNCDSLVYLGGNDEDTFKFMSGLLGKQTIDVRNTSRSFGQ TGSGSLSHQKIARDLMTPDEVGNMKRHECLVRIANMPVFKSKKYNSTKHPNWKYLANQETDERffffDYQINPLNQSQE NHLEGLRIRDLTFESSLK (SEQ ID NO : 1470)>orf02225MSSEQQERMAVQYAERSLLFTVKSLLKILEWSRRQALAQDSAYKIGVQKLEELLQSPYSIDTINLKKD FLDKPIDIEKFKAFLEKEEIPLAIAWQ⑶SLHFYTKDRSILDNHLDQLLEKMVNDPEKLADFTMDKSLDDAIDEAK SQITFRQEGAVKQKEMVR(SEQ ID NO 1471)>orf02226MKVVNLYDLKQMGNKGGCTIQLIHHFPFGMGLGHLKKDYIEFKRVGIVDGKAVEVTLREPYSRDLLQVV KSIKQRQKLIAYRYKEGKLLFVKEEASDVL (SEQ ID NO: 1472)>orf02227MFSNANSFKAKIKNISKDKGIPAQQVQQHYLIEQVLKLISTSSYRDSFIVKGGYLIGQMIGLDKRTTMD LDVTLKGTEMSRENLIHIFEEILCSKTDGFSFSVDKLEPIRQDDEYGGFSLKLNATFDTLKEVVFIDITTCDKITPREITYSMTSIFTNESIKIffTYNLETVLAEKLETIISRGLASTRPRDRYDLFTLYKLRKEEINLEVLKNALENTAEKRK SKDTIYNWEEQVRGIEISDYQKELWIRYQRQFKYAKDISFDNSVQVIREIMQQIF (SEQ ID NO: 1473)>orf02228MVDKREKLMNSFNQYGFLTFKQVIDENLHYKTLLKMVAEGKIDAEEKGLYRLPDIYLDEWFVLQYRFPK GIFSLETALWLHGLSLTIPFNMTMSFPYGTNTKNIKEADICPIILRSHYSEGIIEIERLPGQFIKVYEVERVLVECL RPVHQVDLQIIAPAFKKYFQQNKIHLHKLFYYAQLFKVTDKLQSYTEVLS (SEQ ID NO : 1474)>orf02229MRCLFFYPILKGSELMKTKNQESKGRSPLFKTIKHSFSQ (SEQ ID NO : 1475)>orf02230MELKFVIPNMEKTFGNLEFAGEDKVVQRRINGRLTVLSRSYNLYSDVQRADDIVVVLPAEAGEKHFGFE ERVKLVNPRITAEGYKIGTRGFTNYLLHADDMIKE (SEQ ID NO: 1476)>orf02231MRLANGIVLDKDTTFGELKFSALRREVRIQNEDGSVSDEIKERTYDLKSKGQGRMIQVSIPASVPLKEF DYNARVELINPIADTVATATYQGADVDWYIKADDIVLTKDSSSFKAQPQAKKEPTQDK (SEQ ID NO : 1477)>orf02233MKQRGKRIRPSGKDLVFHFTIASLLPVFLLVVGLFHVKTIQQINWQDFNLSQADKIDIPYLIISFSVA ILICLLVAFVFKRVRYDTVKQLYHRQKLAKMILENKffYESEQVKTEGFFKDSAGRTKEKITYFPKMYYRLKNGLIQ IRVEITLGKYQDQLLHLEKKLESGLYCELTDKELKDSYVEYTLLYDTIASRISIDEVEAKDGKLRLMKNVWWEYD KLPHMLIAGGTGGGKTYFILTLIEALLHTDSKLYILDPKNADLADLGSVMANVYYRKEDLLSCIETFYEEMMKRS EEMKQMKNYKTGKNYAYLGLPAHFLIFDEYVAFMEMLGTKENTAVMNKLKQIVMLGRQAGFFLILACQRPDAKYL GDGIRDQFNFRVALGRMSEMGYGMMFGSDVQKDFFLKRIKGRGYVDVGTSVISEFYTPLVPKGYDFLEEIKKLSN SRQSTQATCEAEVAGVD (SEQ ID NO: 1478)>orf02234LAYGLSQNRLAVATGITRQYLSDIETGKVKPSEDLQQSLWEALERFNPDAPLEMLFDYVRIRFPTTDVQ QVVENILQLKLSYFLHEDYGFYSYSEHYAL⑶IFVLCSHELDKGVLVELKGRGCRQFESYLLAQQRSWYEFFMDVLV AGGVMKRLDLAINDKTGILNIPVLTEKCQQEECISVFRSFKSYRSGELVRKEEKECMGNTLYIGSLQSEVYFCIYEK DYEQYKKNDIPIEDAEVKNRFEIRLKNERAYYAVRDLLVYDNPEHTAFKIINRYIRFVDKDDSKPRSDWKLNEEWAW FIGNNRERLKLTTKPEPYSFQRTLNWLSHQVAPTLKVAIKLDEINQTQVVKDILDHAKLTDRHKQILKQQSVKEQDV ITTKK (SEQ ID NO : 1479)>orf02235MNFGQNLYNWFLSNAQSLVLLAIVVIGLYLGFKREFSKLIGFLIIAIIAVGLVFNAAGVKDILLELFNR IIGA (SEQ ID NO : 1480)>orf02236MNGVFLIFIIQADFLFDFLKVNGKGKPRTDQFALIVFA (SEQ ID NO : 1481) >orf02237MYDVARYYIEETGALGEVPASLQNYIDYQAYGRDLDLSGTFISTNHGIFEIVY(SEQ ID NO : 1482)>orf02239MYLIGYAIKFTPNCCNGFLWLVSAKRYFFSCIGQLWSQCISNDRLQKSIRLFTIKSFCRHKPCESHRNP KVFEKCSLYHGKRGQVAKYHHCKE (SEQ ID NO: 1483)[3400]>orf02242MAYPIKYIENNLVWNKDGECYAYYELVPYNYSFLSPEQKIQVHDSFRQLIAQNRDGKIHALQISTESSI RSAQERSKNEVTGKLKAVAYDKIDQQTDALISMIGENQVNYRFFIGFKLLLNDQEFSMKSLTVEAKNALSDFVYDVN HKLMGDFVSMSNDEILRFQKMEKLLENKISRRFKIRRLDKDDFGYLIEHLYGQTGTAYEEYEYHLSKKKLDNETLIK YYDLIKPTRCLVEEKQRYLKIQQEDETVYVAYFTINSIVGELDFPSSEIFYYQQQQFTFPIDTSMNVEIVANRKALS TVRNKKKELKDLDNHAWQSDNETSSNVAEALESVNELETNLDQSKESMYKLSYVVRVSANDLDELKRRCNEVKDFYD DLSVKLVRPFGDMLGLHEEFLPASKRYMNDYIQYVTSDFLAGLGFGATQMLGENEGIYVGYSLDTGRNVYLKPALAS QGVKGSVTNALASAFVGSLGGGKSFANNLIVYYAVLYGAQAVIVDPKAERGRWKETLPEISHEINIVTLTSDEKNKG LLDPYVIMKNPKDSESLAIDILTFLTGISSRDGERFPILRKAIRAVTNSEVRGLMKVIEELRVENTPLSTSIADHIE SFTDYDFAHLLFSNGYVEQSISLEKQLNIIQVADLVLPDKETSFEEYTTMELLSVAMLIVISTFALDFIHTDRSIFK IVDLDEAWSFLQVAQGKTLSMKLVRAGRAMNAGVYFVTQNTDDLLDEKLKNNLGLKFAFRSTDLNEIKKTLAFFGVD PEDENNQKRLRDLENGQCLISDLYGRVGVIQFHPVFEELLHAFDTRPPVRKEV (SEQ ID NO : 1484)>orf02244 VKPSIVNRIKSNWTLKRLGKVAMTVAFTLVIAIFLLAMLGTVVQAAGLVDDTVNVANEYSRYPLENYQL DFYVDNSWGWLPWNWSDGIGKQVMYGLYAITNFIWTISLYVSNATGYLVQEAYSLDFISATADSIGK匪QTLAGVSA NGFSTEGFYVGFLLLLILVLGVYVAYTGLIKRETTKAIHAIMNFVLVFILSASFIAYAPDYIKKINDFSSDISNASL SLGTKIVMPHSDSQGKDSVDLIRDSLFSIQVQQPWLLLQYNSSDIESIGIDRVESLLSTSPDSNNGEDREKIVAEEI EDRSNTNLTITKTINRLGTVFFLFVFNIGISIFVFLLTGIMIFSQVLFIIYAMFLPVSFILSMIPSFDGMSKRAITK LFNTILTRAGITLIITTAFSISTMLYTLSAGYPFFLIAFLQIVTFAGIYFKL⑶LMSMFSLQSNDSQSVGSRVMRKP RMLMHAHMHRLQRKLGRSMTTLGAGSAIVTGKKGQSGSGSSARTQADHSRPDGKEKSTLGKRIGQTIGTVADTKDRM VDTASGLKEQVKDLPTNARYAVYQGKSKVKENVRDLTSSISQTKADRASGRKEQQEQRRKTIAKRRSEMKQVKQKKQ PASSVHERPTTRQEQYHDEQTSKQSNIQTSYKESQQAKQERPAVKSDFSSPKVERQGNTVQEKTVQKPATSTTTADR TSQRPI TKERPSTVQRVPLQNTRTTNQNRHH(SEQ ID NO : 1485)>orf02246MKLKTLVIGGSGLFLMVFSLLLFVAILFSDEQDSGISNIHYGGVNVSAEVLAHKPMVEKYAKEYGVEEY VNILLAIIQVESGGTAEDVMQSSESLGLPPNSLSTEESIKQGVKYFSELLASSERLSVDLESVIQSYNYGGGFLGYV ANRGNKYTFELAQSFSKEYSGGEKVSYPNPIAIPINGGWRYNYGNMFYVQLVTQYLVTTEFDDDTVQAIMDEALKYE GWRYVYGGASPTTSFDCSGLTQWTYGKAGINLPRTAQQQYDVTQHIPLSEAQA⑶LVFFHSTYNAGSYITHVGIYLG NNRMFHAGDPIGYADLTSPYffQQHLVGAGRIKQ (SEQ ID NO : 1486)>orf02247MMKFRKNQNKEKQIPKEKKPRVYKVNPHKKVVIALffVLLGLSFSFAIFKHFTAIDTHTIHETTIIEKE YVDTHHVENFVENFAKVYYSWEQSDKSIDNRMESLKGYLTDELQALNVDTVRKDIPVSSSVRGFQIWTVEPTGDNE FNVTYSVDQLITEGENTKTVHSAYIVSVYVDGSGNMVLVKNPTITNIPKKSSYKPKAIESEGTVDSITTNEINEF LTTFFKLYPTATASELSYYVNDGILKPIGKEYIFQELVNPIHNRKDNQVTVSLTVEYIDQQTKATQVSQFDLVLE KNGSNWKIIE (SEQ ID NO : 1487)>orf02249MKIINIGVLAHVDAGKTTLTESLLYNSGAITELGSVDKGTTRTDNTLLERQRGITIQTGITSFQWENTK VNIIDTPGHMDFLAEVYRSLSVLDGAILLISAKDGVQAQTRILFHALRKMGIPTIFFINKIDQNGIDLSTVYQDIKE KLSAEIVIKQKVELYP匪CVTNFTESEQWDTVIEGNDDLLEKYMSGKSLEALELEQEESIRFQNCSLFPLYHGSAKSNIGIDNLIEVITNKFYSSTHRGQSELCGKVFKIEYSEKRQRLAYIRLYSGVLHLRDSVRISEKEKIKITEMYTSING
ELCKIDKAYSGEIVILQNEFLKLNSVL⑶TKLLPQRERIENPLPLLQTTVEPSKPQQREMLLDALLEISDSDPLLRY
YVDSATHEIILSFLGKVQMEVTCALLQEKYHVEIEIKEPTVIYMERPLKKAEYTIHIEVPPNPFWASIGLSVAQLPL
GSGVQYESSVSLGYLNQSFQNAVMEGIRYGCEQGLYGWNVTDCKICFKYGLYYSPVSTPADFRMLAPIVLEQVLKKA
GTELLEPYLSFKIYAPQEYLSRAYNDAPKYCANIVDTQLKNNEVILSGEIPARCIQEYRSDLTFFTNGRSVCLTELK
GYHVTTGEPVCQPRRPNSRIDKVRYMFNKIT (SEQ ID NO: 1488) >orf02250 MKPSSFQTTIENQFDYICKRAMEDERKNYMLYLSRIAKREVSFSDVGDYLVSQFATTDNYSTDFQIFTL NGLSVGVENDLLSEALRELPDKKREILLLFYFMDMSDSEIADLLKLNRSTVYRHRTSGLALIKKFMEEFEE (SEQ ID NO 1489)>orf02251LATLDCVQCIYNFFKLFSFNLNTIAIHNQPICIFIFLCQAS (SEQ ID NO : 1490)>orf02252MSEKRRDNKGRILKTGESQRKDGRYLYKYIDS FGEPQFVYSWKLVATDRVPAGKRDCISLREKIAELQ KDIHDGIDVVGKKMTLCQLYAKQNAQRPKVRKNTETGRKYLMDILKKDKLGVRSIDSIKPSDAKEWAIRMSENGYAY QTINNYKRSLKASFYIAIQDDCVRKNPFDFQLKAVLDDDTVPKTVLTEEQEEKLLAFAKADKTYSKNYDEILILLKT GLRISEFGGLTLPDLDFENRLVNIDHQLLRDTEIGYYIETPKTKSGERQVPMVEEAYQAFKRVLANRKNDKRVEIDG YSDFLFLNRKNYPKVQVITTA (SEQ ID NO : 1491)>orf02253MGHANIAMTLNYYAHATFDSAMAEMKRLNKEKQQERLVA (SEQ ID NO : 1492)>orf02254MKRIIPVYIFQQVNVLLVSLYLLKLLCISELTILQILYCASLISFLWMYGQRKQVVKVNMKTRMKWLGI GFVSLLIINLCFSLIHAQGTTNQANLIGLQHQVPWFSFLLLLINASMVEEFLYREILWNLVRKLDIRVALTSILFVL AHHPGTILAWCLYVSLGMFLGLVRYKSDLWGSMGLHLVWNLSVYVLFFL (SEQ ID NO: 1493)>orf02259MKRITANQYQTSERYYKLPKILFEDEKYMDMKLEVKVAYSILKDRLELSLSRGWIDEEGAVYLVFSNSK LMKLLGCSKSKLLSIKKILKEYDLIDEVQQSSSEKGRLANKIYLGELSSTPVASSNRPSVKKKIGQVENETAPVSHS APSETEVSETKYSETDSLFSEDEEERYTQPILKRKVEKVTKYDQDYIWGLVQDQFRREGFSETASEIAMTDFERIYQ YALDNVRFVRRAEVLAEFVFNGLYSVWNNRVRKGGG (SEQ ID NO: 1494)>orf02260MTKELQSSRYIVISFLVREMGIDIVEAISLMAELEKSGLVRLESSGDLILKELGGAL(SEQ ID NO: 1495)>orf02261MIVILLSFFLQKIKKGEQYSTVLQNIFIKKKNPAKLIFGRVFGRKLN(SEQ ID NO : 1496)>orf02276LQVWYNLQSDFEQEITLIMWNPFANLVFNQPLISFFADLNLKILGYSYTDRVKTWPDIGTGCRYNNLHLILLAP (SEQ ID NO : 1497)>orf02314MVICHNDYLLWLPEFSQPLTSLSQTTFFNLNIIRMMRNIDSDFHRRISFSLLVFFC(SEQ ID NO:1498)>orf02318LIEGHLVFADKPAQALVLLRKVGSPKKVSFLTLHLYFLILKIDILKITGF(SEQ ID NO : 1499) [3432]>orf02324MFLHHLLQIKGGLGIQTSQGFVQNPNIRSRQECPNDKDFLTHSVRKSFNNLIAVFSKIKNVQ (SEQ ID NO 1500)>orf02326MTNQAHNLSIFNLQIEITQGLFITIQLTNILKFNHGTTPIFICIIHRYTSTLIQKNQYFILSS (SEQ ID NO 1501)>orf02348MAVTKSQVFSRQGFDFSILGQDLTRLQDVSNLATIGTRIHKDSTANASWNTTSKLKAS(SEQ ID NO: 1502)>orf02349MTEGNASCFNQVSPSFCFNGIAINRNVIELVTQDDKSTNPTITNDDIACIAKNHPRDIFLVGKFHNASQ LKTISffKDQ11SLSTYFCITIAMQGFLKTDINSF (SEQ ID NO 1503)>orf02361MRLRDLRRVDFPDPDGPIKAVISLGWKDRETLFKAFFLL (SEQ ID NO : 1504)>orf02364LKNHSNVFTHFINVDFWTVDINSTIENLPSYFSNINGIIHAIETA (SEQ ID NO : 1505)>orf02365LHINPLNGFIFTIVNMDILSRKGYFFFRKGKDMLLIPVIC (SEQ ID NO : 1506)>orf02387MTIHIQVVKTNMVILADRFFQGLILRSTDKFFIKIRLVRSHNLRFNNMDFSTVAVHENKGRHHVDELLL RFIINSKATVAKKSIVAQGFRFDGNFFRKTRQTNHLNIIFYDNPDQIIFFQNGLITNSQFNRLHP (SEQ ID NO
1507)>orf02404MVKRRIRRGTREPEKVVVPEQSSIPSYPVSVTSNQGTDVAVEPAKAVAPTTGffKQENGMffYFYNTDG SMATGWVQVNGSffYYLNSNGSMKVNQWFQVGGKffYYVNTSGELAVNTSIDGYRVNDNGEffVR (SEQ ID NO
1508)>orf02420MRFIVGRFTSFSLGIEFSPTSKLDDLLFKIAFLMILATWIKARKTKEAT(SEQ ID NO : 1509)>orf02424MANDNKSHYLIYRVLGISFEEGENIDLYQNKGRFLYKYAGSFLEEAAVLSFNEKFGTENT(SEQ ID NO 1510)>orf02433LHYRTTPTLIMVVQRDCLILSFPRQKGPIVGQMAIIL (SEQ ID NO : 1511)>orf02435VFALLDNSTFLRKSLHLRKMEMFPVETEEITYKRKKSKGKRQAILAQFDSEEVHHQVEESICPDCQDDL KEIGASLQRQELVFIPAQLKRVDHIQHAYKCQTCSKNNPSDKIVKAPIPKAPL (SEQ ID NO: 1512)[3458]>orf02451LVCQTIKYWHKFHLHIGRCKLLIGLIPVLNFFIRADIDCLLVLLSLIDRQNGKQFNLCQWIIASNGLND SFEIIESLIHRNILSDIICPNQKKNFIYCSTI (SEQ ID NO 1513)>orf02459VGHNSGSFFLFLLLRLLLSPLLRNSISFLTSQGIPWKLSNNKTKPIDKPTASKSIATNPLLLHLR (SEQ ID NO 1514)>orf02480LDFLNHLWVAHAGNSSSCTNISRNSFQGHHSCRTSSFCDTSLFRILHIHNNTTLEHLCQVFI (SEQ ID NO 1515)>orf02505MLLLISLTQLIIFLFFERFNLLLKTFLLVDLKSNKSA (SEQ ID NO : 1516)>orf02517MGFSMKLIHDLNTHTTHSTAKMLHNVKAIKNDFSIRE (SEQID NO : 1517)>orf02524MQEHYTPKGKHLTIDNRRLIERWKNENKSNREIAGLLGKAPQTIHTEVKRGTTLQQVRKGLYKKVYSA DYAQTVYQFNRKRSVKKLILTKEIREKILHYHKQKFSPEMMVNKKQVKVGISTIYYffFHNGHLGLTKADMLYPRKR KGVKKQASPNFKPAGKSIEERPDVINLRLENGHYEIDTVLLTKIKNYCLLVLTDRRSRHQIIRLIPNKTAESVNQ ALTLLLGEHRILSITADNGSEFKRLSEVFPEEHIYYAHAYSSWERGSNENHNRLIRRffLPKGTKKTTPKEVAFIE NWINNYPKKCLDYKSPSEFLLGG (SEQ ID NO: 1518)>orf02527VVPRYVTKHQGffDHNSHTITNSDDDPATLVTFRTFKFNVGNCTIPKNDQNGSSQKFSGIL(SEQ ID NO 1519)>orf02534MAYSTDFKQRALDYIKEGHSHVEAAKFFGVGVRTLFTWEKKDVNKDT(SEQ ID NO : 1520)>orf02585MAVQANWSFDITHDSSFFFSNQKRGLNFSQMCFKDRRRNGFFDRKIFKFKFNNPIQIF(SEQ ID NO: 1521)>orf02595MEIVLVSFSISFQHFIIAYCLDFSSAGFRNSQNFSNFC (SEQ ID NO : 1522)>orf02608MKLKLLRVDTKVIMGSFLLVLSSLLALLLPLILKGLIDGSSIENIGSKVFQSFLIFIGQALFSSIGYYL FSQSGEKKIAKIRKKVIEGLIYAEKSFFDKSQSGELTSAIVNDMSVIREFLITTFPNIILSLVMVLGSIVVLFSLDff NLSLLLFITLPCMMFIILPLSNISEKYSRRLQEEIGFLTGQLTEKIQEHELIKTNQAEKSVQDVLDNCIERVQNNSL KSDRVTSFETPFALLFIFATIVVMLTYGGYRVSAGYISVGTLVSFLIYLFQLLNPISNIANFVTIYSSSKGSSVALE NLLAVPKEKFEGGKSVSGQGLNFNHVYFGYDENRPVLKDITCSIFKGQKIAFVGPSGSGKSTIVRLLERFYKPLSGD ILMEQSSIYDFNLKEWRSKIAWVSQNNAVLSGSIRDNLCLGLNRLVTDDELMKVLDLVSLGDEIRSMKEGLDTEVGE RGRLLSGGRSQRLQIARAYLKDAEILIFDEATANLDADSEYAIISSLYSVLKEKTVVIIAHRLSTVKDVDCIFFLEE GKITGSGTHKELLENHERYARFVQEQMIE (SEQ ID NO : 1523)>orf02621[3481]liryldqyedvilreikaqfpdvavdklmeeyikaglilrenkryylnfptlesldsleldqeifvrea spvyqalleqsfetelrnqinaailvektdfarikmtlsnyfykvkqqypltekqqelydilgdvnpeyalkymtaf llkflkkdqlmqkcrdifvdslvvlgyivqnedgkyelaidfdkerltfyla (seq id no : 1524)>orf02622 miglkevcrfltdntslstsminhpiqingnmaivtcgsldglshv(seq ID NO : 1525)>orf02633MRERVRLSGSLFTSLKTREHIKSTMELFHKYVFFLIQEIKIKMINFLKIGDLPTL(SEQ ID NO: 1526)>orf02643midhfeikvkdlqisegfyrsflapldyklafktsslisflspnsphpggdfwltqgtqdpvhfaflae nkeevqacyeagleaggrdngapgyrsehpiyyaafmidldgnnievvchke (seq id no: 1527)>orf02645vivflsrnkdgnafchldlisianpvwgwdddfitwidhshkegierifgsrsdchli(SEQ ID NO 1528)>orf02648lsnqfyfslqtkpilkvkqfllfqsqmirvseilqfsnkl (seq id no : 1529)>orf02652MKHSHKKSFDffYSMQQRYSIRKYYFGAVSVLLGTALVLGAAASVQTVQAEENKQETTNSISVGRGEAAT kpaevsasnkektyaaptvanpvettpvktgevtkpaekveeakdkkeevthqdaidksklltalsrakklesklyt easaanlqtsiqagqsllgkadaseaelsaaessiqssiiglelrsnsnkgtvsetpvakkaniveakeetkpavtt tersavdsailpistaakvettsapastneilkpslslsdarqnpairkedvdrgysgfrtagsgfraagsgfraag penkpilnpnntiafsdisqglhsfrgighsrggreihydvttvrrgnrlnftikysgpgefvnnnfildkgdgfgn psnatitssnprvreqsksisqganyvshsgysmtsatstnteqtirfslpiinpngdlsvrlkpvtfnvdqgggga atsndpysnsnyyhranpllldanpyggtnnktvsedidfqtvylptsklpegqtrlvregekgqrqitykvhrfgn etllglpisnrvtkeakprimqigvakelidtvkprvdqnkvgdtnnltfyldndgngvytegvdelvqkiaikdga kgekgdqgergltgaqgtkgekgdqgergltgaqgakgekgeqgfqgrdgeqgpkgedgktptvkvtdgqdgthtit indgkggitttwrdgfdgasplvsthrneadktttvifyydlndnnqfdegdtklkewiadgkqgpkgdk ⑶ ngk dgftpevtvtdnnngthtititqpdnrpslttivkngedgktpkvkaerddakkqttltfyidkdgdgsytagkdel vqttwkdgqdgaagasgrdgkevlngkadpttegkdgdtfvntqtcdvfvkkgntwepagnikgpkgdkgadgakg EK⑶RGERGLTGAQGTKGEKGDQGERGLTGAQGTKGEIffiDRGERGLTGAQGQAGRDAVTPTVTVKDNKNDGTHTITI ndgrgnvastvvrdgfdgasplvatqrneadktttvifyydqngnneldasdkklkeviiadgakgeqglqgrdgqd gaqgqagrdgkdvlngkanpevnqgkdgdkyvntetcdvfvknngnwdkegnikgpkgdkgergedgktpevtvtpg
kdghstditftvpgkdpvtftvkdgkngkdgrapkikveditspsrirrdtdaaatptrngirvtvyddvndngvyd
egvdkvlnskdiyngidgrdgsaptittkdngdgthtitvqnpdssesttvvkdgkdgktanitttenpdgshtitv tnpdgstketvvkngkdgktpkvevtdnndgthtvkvtdgdgnvtnaiikdgkdgkaatatttenpdgshtvtitnp dgtknefvvkngrdgvdgrtptasvrdngdgshtivitnpegvttettvrdgkspkvtitdeqngthkisvlngdgt ttetiikdgkspvatvrdnqdgtytirvengngtvsettvrdgksptakvvdngdgthtitvvnsdgttttttvrdg repklevidnndgshtikvtgadgkgttttifdgkspkanivdngdgthtltivdsdgreyksiikdgkdgkdsvsp tvtvknnndgthvvtitnpdgsktemvikdgkdgkcgcqdkpvtpsndkpvpptpnvptpevpvkpvpaqptpnvptPEVPVQPTPAVPTPEVPVKPVPAVPEQPVVPTPAQPATPVNANPVAPTTGKENRGDKLPETGSQSDYISVLLGSGIL LSLYVGRRKED (SEQ ID NO : 1530)>orf02654MRNLLSTKVQRQLRLMETLIQNRNWMKLHELAEKLGCTERILKSDLNELRIAFPSINIQSSVNGIMIDL EVNTSVEDIYQYFLANSQSFQLLEYMFFNEGLPIYRTIENLYFSSANLYRLGRNITKVLSSQFQIELSFTPSEIRGN EIDIRYFFAQYFSERYYFLDWPFPDLPEEDLTEFADFFYKITNYPMRFSIYRMYKLMIAISIHRVKNGHFIDLPNHF YKEYYPLLKSIPNFQETLAYFSKHFGLEMTPDTIAQIFISFLQNDIFLDPQEFFNSLEDNSQARYSYQLLSQILERL SKQYKITFTNHDELIWHLHNTAFFERQEIFSTPILFEQKALTIKKFEVYFPDFMGSARQELAQYRQAIGQHDHPEQL EHLMYTILTHAENLSTQLLENRPPIKVLIISNFDHAISLTFVDMLSYYCNNRFTFDIffDELKTSPEILNQTDYDIIV SNFYISGITKKFICRNHLSIMNLVNHLNTLSNEIHLSNTL (SEQ ID NO : 1531)>orf02655MIFKIGLFYLGQFVSLDMTVHKPIKKLQGWVVLSSLPFQSLDILTFFRSLLS(SEQ ID NO : 1532)>orf02657MGFYLMVASMLLGLLALKIGFSQFKENKDKFLSILTSLAGLALVLVAVffLGffPK(SEQ ID NO:
1533)>orf02677MLDSDIGCSRKNLLGLFWIRRRRNIHIVDRAMEKGISNRAPNKISLKACFFNFF(SEQ ID NO:
1534)>orf02696MAFNQFNRCITLSIPTAPNIPTSVVHRTYLHDATVPNNVREKT (SEQ ID NO : 1535)>orf02698MQQITEIIIAFATSFLTVAVGGIVKAVKDYLLRKGGEKAVIIAEILAKNAVHAVEQVASETGYKGEEKL EQARAKVRAELTKYNISMTDKDLDTFVESAVKQMNDAffKGR(SEQ ID NO: 1536)>orf02699MKIEFFNFLRSVIQTEDGLVLYALALIVSMEIIDFVTGTIAAIINPDIEYKSKIGINGLLRKISGVLLL MILIPASVLLPEKTGFAFLYSICLGYIAFTFQSLIENYRKLKGNVTLFQPIVKVFQRLLEKDDDTKKGE (SEQ ID NO 1537)>orf02700MLKVTKTRQLVTEFFAQD⑶QQKLVKTTVINTDNKAVSTISETLHDPDLYANNRISMRKHEQELREMRY KIEDAILAELEADSEHKE (SEQ ID NO: 1538)>orf02702 MTKFINSSGSLHLNIYIEQVSQDIANNSSRVSWKATVDRDGAYRTYTYGNISNLSVWLNGSSVHSSHPN FDTSGQEFTLASGEVTIPHSGDGTKTFAVWASFDPNNGVHGNITVSANYTLSSIPRSSSVSDNALSGNRRLGSPHTL TIDRKSSSFTHQVWYRVFGSNWIDLGKNHATGVSFVPNIDLARYNTKAKSGTMDICVRTYNGTTQVGNDVYSNGWYF EIPESVKPTFSGItltdmntvarqllsgnnflqIISDIQVNFNNPSGAYGSTITGYRAEIvnknqvttvnggrlgmm NFNGSATIRASVVDSRGRQSDTRDITINVIEYFAPAFSFTAFRTRETPNIIQVVRNAKIAPITLSGSQKNVMTLSFK VARLGSTTFTADHGRASGIWTTQHTLNNSAANMAGNYVATKSFVVIGTLSDKFTSTEFTATVATESVVMSYDKDGRV GIGKVAEQGGAGSLDVLGDIYARNKPIQQYQLTDNNGCGKLIKQDFNTMKETGTWWINGSSQNNPFSGTWGMLEVFR PNPGSHERIQRFTTSTGYMAVRENGYDNNWRPWRYLVQQSKSTNNSDYVALLKSESTPTPWQNAILQNGWNHHRDYGGVQFSKTFDGVVCFKGTCKGGKIARESIILTLPEHFRPSTTLFKTALNNDYGSAVIGIYPNGNVVVKSNVDATWLNF DNVFFKI (SEQ ID NO 1539)>orf02709MLLTIHDANLQKVAFIDNEKQGTLNYYDDTWTRSLATGSSTFEFTVFKKAVKSDLPLAKAYHHLNEHAF VSFKYKGKSFVFNIIIVEENEQTIKCYCENLNLELINELANPYKSNKAMTFKEYCEAMDLLNYTHLSIGINEISDYK RTLEWEGQETKLARLLSLAKRFDAEIEFDTQLNADSTIKKFSVNVYHENDDNHQGVGRVRNDVIVKYGKNIHSITRK VDKTGIFNTIRPTGKMPTVEEELS⑶KGSKSETVKNADGSTTKTTISTASDGTKSKTIVHTKVTKLADKTRITTTTT TRSDGSIEQTVTTSKKGGASTSETKVLKKPNPKEKTNTTEDVLTIEGLDEWEVKNEKGIVEFYQRGQALYAPISMQL YPSTFTHSTGELDQWTRKDFHFETDEPNELRRLGYLKLKKYCYPAITYEVDGFVDADI⑶TVKVHDDGFAPLLMIQA RVTDQKISFTNPVRNKTIFDNFKALENKLSADIQSAFERLFEAAKPYTIKLSTDNGVIFKNQIGQSLVTPTLYKGGK PVVVGVTWRWALDGEVTTGMTYLVRGSNVTDTVTLTVAAYIGNKEVAVDEISLVNVADGKLGTPGTPGRDGRTPYVH TAWANNATGTDGFSLDSSINKLYIGIYTDFEPNDSTDPKKYKWAKVKGEKGEK⑶KGEPGQRGLDGLQGARGEQGLP GRNGADGRTQYTHIAYSNSADGTKDFSVSASDRAYIGMYVDFNRADSNTPSDYNWTLVKGSDGANGVAGKAGTDGRT PYLHIAYATSNNGSQGFSTTDSTNKTYIGTYTDYTQADSTDYRVYKWTLIKGADGTGISNVTNYYLATTVSTGITRT SAGWTTTPQPITSDKRYLWNYRVELYTNGTSKTTEPTVIGVHGEKGERGLQGLQGLQGARGEQGIPGPRGADGRTQY THMAYADNATGGGFSQTNTDKAFVGVYIDFNPTDSRNPADYRWTRWKGRDGANGVAGRAGADGRTPYLHIAYATSNN GSQGFSTTDSTNKTYIGTYTDYTQADSTDPKKYKffAKVKGDKGEKGDKGERGLQGLQGLQGARGEQGIPGPRGADGR TQYTHMAYADNATGGGFSQTNTDKAFVGVYIDFNPTDSRNPADYRWTRWKGRDGANGVAGRAGADGRTPYLHIAYAT SNNGSQGFSTTDSTNKTYIGTYTDYTQADSTDPKKYKffAKVKGDKGEKGDKGERGLQGLQGLQGARGEQGIPGPRGA DGRTQYTHMAYADNATGGGFSQTNTDKAFVGVYIDFNPTDSRNPADYRffTRffKGRDGANGVAGRAGADGRTPYVHFA YSENADGSGLTMTDNGQRYFGHYSDYEKPDSSDKTKYKffADRWAKVDGGYVNIYALSKNRSIGKSYHVSEFNMDVLS GNITLKAIGSDPYIGAVSSHPGIFIKQQGMKIPVIQGRSICITITNPLFRKNYISFFNSLGKTVKTYKHYNTNKFLI SSADLVGVEFIALRYGAGSSNIQIGTVLETKVKVEYGTVHSDWSPAPEDIESNINSKADQGLTQEQLNALNEKSQIL EAEMKAKASMEAFSELEKAYNAFVKSNADSRKKSESDLVEAGRRIDLLTTQFGGLAELKTFIDTYMKSTNEGLIIGK NDASSTIKVSSDRISMFSAGKEVMYISQGVINIDNGIFTASIQIGRFRTEQYHLNKDVNVIRYIGG(SEQ ID NO 1540)>orf02711MTKIMTFNGVDMSKFFRITDIIRPIGNKRSVSTDNAPLLGVNIQQVKIGEKEHIIKFDIKTTNAIEMEQ LKHDLAGILNVLEPVKITY⑶EPDKYYMGLPVDEITPENLTRWFQRSELKIIIPDGVAHSTTLKNFDIDTNETSAPD RIVFNLTNTGTEPAYPIIRIKHNSENGYIGVVNNRAAFELGNREEADTEKYRDSETLIDYRGTNILKGFQNGTKGVA VTNDNKERLVGTLSTTSMWGRNHIELSNRGTVEKNRNNAQSLTWAIPVDSSGEVGSLNDYLLWRQVFMAAVANQYGF IKVTVSDTDGNFLYGVETYKRYQTLDCEYSFFTTDGKGGYKFIKWWYFTGTGAQVGKLDPFSAEKGWSELKRNDDRV QVFFDGSHYDFIIPEIKDKKSAKIHITLGALRDWPLVSHMYVDEFMYRKDFVTKSRDIPNRYPIGSNVVINSEDDSV YIDGISKVSEVVDGSHWPAIPPGKSQLELYFSRFVKKKPTVTIEFEERWI (SEQ ID NO: 1541)>orf02714MADGKVTIVVDVDGNKVKVLNDELDKAAQK⑶RGSDSLKKFAIGGAAFKLASKAVDLLTDSLGGAIQRF DTLESYPRVMQAMGHSTEDVTRSTKKLAAGIEGLPTTLNEVVGTAQRLTSITGDINKSTDLTLALNNAFLASGSSSA DASRGLQQFSQMLSAGKVDMQSWKTLQETMPYALQKTADSFGFAGQSAQNDFYSALKEGRITFNQFSKKLVELNGGV GGFAELAKSNSKGIQTSFGNLKNAVVKGVANTIKALDDLTKAATGKTIAENFDALKVIINAAFGVIVNVIKASTPVFQTLFSILGTGASVISSLTPVIISLVSALVAMRAANEAITATKNLINSWQTFKTTATGAIQIINLMTAAQATCGSVTK AQLVANLANNGALTASNLLYGVLTGSISLQTAATIAATAATTAFKAALTALTGPIGLVVAGVGLAVGALVGLWQWLT AESEETKRLKSEQEELVKSTDQLTDSVKQSAKERQKNLESVKGNTESYQKLADEIVQLSQKTNKTAADKKNLKKKID ALNASVSGLNLVYDKNTDSLSHNNDQIKARISAMEAESTWETSQKNLLDIEQKRAEIGEQLKQIAEQRKKWNEESNV SDSVRKERLQELNDKETELKNTQTELQTEYEKTSQVQQAASEAMAAAAENGSNRQVISYEGMSKAQQKAVDDMRSKY NELLETTTNMFDQIQMKSAISVDEMIANLQKNQEAVNNWATNLNTLAERGVNEGILAKLQAMGPQGGLYVQELVNAS DEKLATLNEVFTQGGESAMNGLTAGMDTGALGITDKIKGIVQSQVSSLQEEIAAADFPEKGKNIPEGV⑶GIKAGAE IASEASKNMANDIKESFTSEMDINSPSRVFNEYGGFITTGLAEGVDKGTNQPVSSVTNLANQIKKPFDSLQSDFTYI GEMAMSGLNAGLWSGSGSVMATANSIAERVKATIKSALDIHSPSRAMRDEVGRFIPQGIAVGIEADAGVVEKSMLRL KESMMIDTRPEIALGLNKKLGAQVTVKQSSKQTIAEKIKVTMDKSSELLEKALDVAETAVRRPNEMYLNDGTLVART GDKFAKYQSEQLRRDNRMKGVLS (SEQ ID NO: 1542)[3518]>orf02715MSMKLNDALITNFSIADKEYDIDLSFNKVLDVFEILKEDEMTRLEQAQLIVHLLTGQELYDIKEVVDCff IYIKEHFLGIEKETVQYDLLGNPMPKAKGEEEQEKLIDFEQDAEYIYASFLQAYGINLLKVQNELTWTEFKALLNAL PDNTIMQQIIEIRAffKPEYGGDKNKMRKLQAKYSLGKEGEDNG (SEQ ID NO : 1543)>orf02717MTDIQIELKRTGFPVKIGEVELWFDTSQESLMCFYDMEEELKRRLVQYELDVVSANINNKIERDGVTK EVVAGAIELEKKQLEIQYDLIFGDGTFDKLYSIYPDYNALNNALEQTAIMLHDKLEEVAEQHKTVVKERASHYLNK GKVTPIKNNKKQKKNKKK (SEQ ID NO : 1544)>orf02718MTRQKNALRGHFVAPYNGGTEPSTEDTWLELAKWISDVSDDTDEKTDDQAYYDGDGVEETTVVSVKGA YTFEGTYDPDDKAQALIAGMKYKTCDDRKLWHKVVSSDRKKQWVGAATATEIKAGSGAASDYEAFGCKLSYNSTPK ETGIG (SEQ ID NO : 1545)>orf02719MRENDFQNVLLKHIKTLNLPVEPRFDYFEDDKDDLVINQIPGGKVDREYMDGTQEVSLPFEIAVKAKK NSVANDTIWLVTSELAKIDLVLPSDNNSYEYMGMEVSRPAMKGKDEQGYYYYTIEIVAKIVIERNKQ (SEQ ID NO 1546)>orf02720MNIAIKVDLQKAKQKLSNESMTRGKIAVASKILLDNEQYIPLRGGELRASGRIVGQGDAVVYGTVYARA QFYGSNGIVTFRRYTTPGTGKRWDQVATSKHAEEWARAFVKGMGL(SEQ ID NO: 1547)>orf02721MTYLTQEEFDELDFDEVTDFEKLAKRAKIAIDLYTNGIYQKDIDFEKEIAYRKSAVKLAMAFQIAYLD ASGIMSADDKQLANSVSIGRTSISYSTSQSTLAGQRFNLSMDAENALRQAGFSLVVGVAYDR (SEQ ID NO 1548)>orf02722 MALYKATKNLFFEQLNMDVIVDD11ELDEDYAKEVNKKLKNAFPDVKNVLELVDKNGTLEPEDAPSVDD ASQATVED (SEQ ID NO : 1549)>orf02723MPSNQNNAVRRYEKQYAGILETVFGVRAAFSNALAPIQILDGVQENSKAFSVKTNNTPVVIGEYKTGENDGGF⑶NSGAQSRFGGVTEVKYENTDVNYDYTLTIHEGLDRYTVNNDLNAAVADRLKLQSEAQTRTVNKRIGKYLSD NATKTEALADFTDDKVKALFNKLSAFYTNNEVTAPITVYLRSEFYNAIVDMASVTSAKGATISLDENGLPKYKGFTL EETPAQYFETGVIAIFSPNGIIIPFVGISTARVIEAENFDGVKLQAAAKGGTYTLDDNKKAIYKVTGTIV(SEQ ID NO 1550)>orf02724MAFTTEELLNLGLTEEQAKSVFALRGKELNEDKSALETIKQERDSLKSQLQKAEEQVEHLKSLENISAE QKDAIDKLQAEYDKYKNEAAAELAQTKKVSAISLALKDTNAFNPDKLMKFIDVDAIQLDDNGKPQIDEVINGLKESD PYLFKAEESKPSPNILPQGNPAGEGTSDVDPFQAIIDGYGK (SEQ ID NO: 1551)>orf02727MKKKRKQITFNDQQFPLQMQGVGDIYEKLQIDIFDRMIKRLKERGSIDLMRNPYIWQLEKLNDMHMLNE QNLKLISERTGIAERLLRDVIENEGLKVYKDTKQQLEEDLNKIPEGEISNGVTDSLEAYSRQAVSDLNLINTTLPKS LQVAYKSIVEETVAQVVAGTKTSDVALHDTIMKWQKNAFTGFVDKGGRHWKADSYARAIIKSTTYKVYNEMRTRPAE ELGVDTFYYSMKAMARPACSPLQGQIVTKGTGREIDGITIYSLLDYGYGTAAGCLGIHCGHYLTPFIVGVHELPNLP DYLKNLTPEQAEENARIEAGQRGLERLIKTHKERLHYAHTLQDDKMIQAERLKVRGYQTKIRNLINQHDFLTRDYRR EKLYIS (SEQ ID NO : 1552)>orf02728MSLFQKVKDFFSRGRYYMQTSNLNSILEHPKIAVTQEEYDRIKRNLVYYQSKWDDVQYKNTDGDIKSRP MNHLPIARTASKKIASLVYNEQATITTKNEILQKFLDDMLTNDRFNKNFERYLESCLALGGLAMRPYID⑶KVRVAF IQAPVFFPLESNTQDVSSAAILTKTIKSEGRKNVYYTLVEFHEWVTADGQETGSTNDKKYYRITNELYRSDVNDVLG QRVNLSELDKYKNLEPVTVFENLSRPLFTYLKTPGMNNKDINSPLGLSIFDNAKTTIDFINRSYDEFMWEVRMGQRR VIVPEHLTQRQYQRPDGTIDFRPRFDVEQNVYMQIGGSSMDAGGITDLTSPIRANDYILAISEGLKLFEMQIGVSSG MFTFDGQGMKTATEIVSENSDTYQMRSSIVALVEQSIKELCVSMCELGKAVGVYSGEIPELDDISVNLDDGVFTDR HAELDYWAKMVAAGFSTKKRAIGKTLNISGVEAEKELNAINSELLPMNDAELAIYGMHDQNEEKADDKG(SEQ ID NO 1553)>orf02730MTFNVQKNINPHFKSVWISSLPYNVLKGGRNSFKSSVIVLKLAYMMIRYIIAGEAANIVVIRKVANTIR DSVFNKVWWALNLFGIAEQFTKTVSPFKIVHKTTGSTFYFYGQDDFQKLKSNDIGNIIAVffYEEAAEFNDQEDFDQS NVTFMRQKHPRAKFVQFFWSYNPPRNPYSWINEWFESIKTNKNYLAHSSTYLDDELGFVTEQMLEDIERIKENDYDY YRYLYLGEAVGLGNNVYNMSMFHAIDALPSDDKLIGISFALDGGHQQSATACCAFGITAKGKVILLDTWYYSPAGQV VKKAPSQLSKEIYAYMRSVIEKYRVQALQYTIDSAEGALRNQMFLDFGLKWHPVAKLRKVTMIDSFQSLLAQGRFYY LNTENNKIFIEEHKMYRWDEKTIKSDNPSVIKEDDHTCDTTQYFVLDNAKLLGLRVGNV (SEQ ID NO : 1554)>orf02731LPRDGTKNLKPVTERTKDEARAISSKGGKASGIARRKKADLKKAFETLLSLDVTDSKIKKQLEEMGMA GNNEALLAFATFQQAVKGNQKATENIIKLTNTKDKYDIQEQKERIKALKYENRERAEAEKGSSETIEIVDAWAEDV RGATDDL (SEQ ID NO : 1555)>orf02732VAQKLTKLKDIFKHVSSIDLGKEILFEDLELYNKETETSKQYQSIEEAENDLYLMEKVNKINFTLGGGR GANFEKGKDGKYPGFRGAGGARDSGSSKALHPASLNNQGRFSSVEGAIQGFIKKHGGSRTEYSTAVDSQGFAHNYVH GGKNSVQILPISGGFTAIHNHPNGSNFSSTDLHSFAALKGMNTLVATNSSKAYRITKGANFDAKGFDKAVSKSRFT TKDYNKGADLffLKKNAKKYGYTYSYE (SEQ ID NO: 1556)>orf02735MLQIEYVDIKSIKPYHKNARHNDGEATEKVAASIKAFGFQQPILVDDNNIIITGHTRLKAALSLGIDTI PIAHAVNLTDEQIKAYRLADNRVAEYSTWDSELLNIELSQFETIDMAQFGFELSVTGFNFGNEEEQQEETENEEEDA EDFHRDTTINQYNLFNYDDTRVEGFYNMPKIEGVDHIPKDFQGFNYVLNKPDYSSCVHFFLDDYQFERIWQRPDFYI EKLLEFDSALAPDFSLYLDMPIAMQVffNIYRSRLIGQIMQDYGLTVIPTVSWASEESFDFCFDGLPKNSTLAISTI GVKQNKEQFEVWKNGVTEMIKRLTPKRIVVYGGKVEYDYKDIEVVYFENATTERMKESGTKTN (SEQ ID NO 1557)>orf02736MNVIGACQKILFYSPTQAYVLLNAWFNDYFRATYTELLENAILDK(SEQ ID NO : 1558)>orf02738 MNPEIIDNINKPSHYQGANGLEAIDVVHNFVGSLSGASAFFWGNAIKYMLRFQKKNGLEDLKKARKNLD WLIEEMDKEGR (SEQ ID NO : 1559)>orf02739MFFQDSEIEEFELNDTLRNDYITAYPDEIELMQSTGLKDKNGKEIFEGDIVRTTRFLGRADEIGGFYEY EKDYVGVVKVLEGSWVIDTGSVAVRLWSEIDESEVLGNIYENLEFLEVNE(SEQ ID NO 1560)>orf02740MEDEQNILETQLILGKQVLEIVLDLLKDDSKIGVVLPLNINDREFTITVEKEVTDRD(SEQ ID NO: 1561)>orf02741MTQTLEEGMKNQSKCIKIPMEIRPFDVGYRIVNKHGQALALKNGASIFALPSLAEKAIKKEFGKNDPDF DIEKHFVEEVAIVNLSKFHSYFEEVE (SEQ ID NO: 1562)>orf02742MNIKALIKKYEELWNEHSPFYEPVPYTSMVELFLKELKQLDEPEKVKVPRFVAEWIEEARKACKDVVE LFEFDFTNDEVRKWFMQERPFDLVARAWLDGYEVEEEKRYLVTLKNRQPLVKSQSGSTLYFSQDITARNYKGTQKE LEDANFGffVFDCEGIEIEEVE(SEQ ID NO : 1563)>orf02743MMEELKQKVNEVYNWTVEDGKPQPPKQDLPQAVKERVDYFffEMAEDGMTFMGAMECIFADEKPTDYDLG ATKDWLPKSKEFDDWIGYAPSMAQVVIAVYLIYRGN(SEQ ID NO: 1564)>orf02744VIEVNIKFDNFEAHGFYQDDTKLGKIRDAIISQMNNGHVVVLGEDRGILLNPKVIKSVQFKVVEDNQI (SEQ ID NO 1565)>orf02745LYPTVKAIIDGMTDAGIWTDDNHKVIKKLSFVYGGLSEEKGHYRLEFDIEEV(SEQ ID NO : 1566)>orf02746MTTENLKSALEYAVELNEHGLEILTAADGTEYYDANKFNLKELDPKRYPKTLELSTLTSLVDYLKTDLN NLKNQRLIVAVEKNDEVCVWSENDEIEHRTLLVDVKARIPELSFGRFLSLEQFNIMLQSNFIDDNDRGTLLEFASAL KIENGAEIEDNGVSQVAT VKTGVASLAKGKAPNPVTLRPYRTFSEVEQPASLFVFRIDKQANMALFEADGKRWVADA VGNIASYLKEQLADQKHITVLA(SEQ ID NO : 1567)[3568]>orf02747MDKKLIGLDLTHIADGGLQEKLDKELEKVFDNILDLNTDAKAKRKVTITLTMSANEERTVVDTTMEVKS KFAPQNGVATTILIGRDFDTGQVHANELKSTVPGQMYFDENGEILTDIGQPVAEIEQQAETKSDIIDFNKKKVGN (SEQ ID NO 1568) [3570]>orf02749MESAGHECIGFCEIDKFARASYKAIHDTKGEIELHDITTVSDDTIRGIGHVDVICGGFPCQAFSIAGNR RGFEDTRGTLFFEIARFASILKPRYLFLENVKGLLNHDRGNTFEVILSALDELGYDVEWQVLNSKNFGVPQNRERVF IIGHLRGGSGRKVFPLS⑶GMITCEQPKINKVGNTRKKGKSQS⑶VVSIDSLAPTLCSTTTQKDPLKVLIENEIKQ FGVLQPNYNQSGWYEIDGISPTIRAYQGGNLEPKIRVKEATKQGYQEAEI⑶SVNLSHPNSKTRRGRVGKQIANTL LTGESQGVVEPDFRIRKLTPRECWRLQGFPDWAFDKAQEVNSNSQLYKQAGNSVTVNVISAIAQGLGGN (SEQ ID NO 1569)>orf02751MINNVVLVGRLTRDAELRYTQSNIAVATFTLAVNRPFKNEAGEREADFINCVIWRQLAENLANWAKKGS LIGVTGVIQTRSYDNQQGQRVYVTEVVASNFQLLESRNSQQNNQGHQDHHGGYQQQGYSNQGSSFQNGNSYGQQGSF VEGNTTNLVPDFTRDNNPFGRPTNPLDISDDDLPF (SEQ ID NO : 1570)>orf02752MRCFYVSGKIADLDLGSEINAENSFMAAIEFVKRYTDLLKFGSNEIKVSEVEEVQNDK(SEQ ID NO: 1571)>orf02754MVKDVTNSLTEIKVDFQPAVINVDREAIEAQVAAAIAQYSGREVTVDNYKEVYEERTRFNKLIGGLDTQ RKDFNRQINEPAKDFDKWVKEKVIKPIEAVTDAMSAGLNAIDEHERLMRVDVVRATFEDKCMVAGIEKSTFADKYDE YSLKKYFKTGKYELKKTTLDEMDGLVLSEFDALEEYKANKQAIQEQAQEYDLPADSYIRHLEDGKSLVDILKMMKTD RDAEIARKEQKEIQEKAKAERLEEIAQSAKKNANANIKAYDAETGEILEQGTITPEPQNNAREVAKFEPSEPLVKLV RLELHGGLEQffENTQEYFEDNFIGFETLED (SEQ ID NO: 1572)>orf02756MADLTFAELQRKMQIEKQTKQGVKYPFRTAEDINNKFKSLDSGffSVSFPEDDIIQIffiDKLYYKAVAVVK RESDGTIEKAIGWAREEDVPIFHTQK⑶VKQMQDPQWTGAVGSYARKYALQGLFAIGGEDVDEYPVEESQEQGQNNQ QQKPNNQQAQGQNQVRYIDNTQYQEINDLINDIAKIKGMPFDTLANYVLSEKLKGLQDFHRVQVGDYEVLKNYLTEQ LAKAKAKAKRGN(SEQ ID NO : 1573)>orf02757 MPNWAEGTLKLRGRRENVASALKEMLLGNKGATLEEEYDGTLLI FKNEYDYFYINGTRRAFISSKDIE IffLDDDFVIIELEDFEQAWAALADNYTEISSKFDVDIKIFTFEMGMEFTQEIEISKGEIIKNIVNENFTNYSWDVPF SRLGG (SEQ ID NO : 1574)>orf02758MKKIATAMNVSVSDLFTQDTPIKKNRHSTPVNPKIYKEFIDNVNQYQRLTGATYEKISNIIGKSNSYIY DVIDKQRKSTLSIKSNASLTKGSMILRQEIEKIESGKNRIPSKLTYQTIDRDSEVVFRFNGLIKSVNELSDKELQII VSIFDALKIPAKISKIEIRETNVFGGGK(SEQ ID NO: 1575)>orf02760MKKLPSQQKYLRNDGQLVTIKGFDAYLQYRGSQSWKKEMAKTVKMTR(SEQ ID NO : 1576)[3586]>orf02761MPDITNGREKVNDFLKDKGIKKTSLAIAYGFKRQEVTNILSGTTKGPRANSFILQVIEDYGIE (SEQ ID NO 1577)>orf02762MFETFEKIKSLAKKQGISLNTLEDRVGLGKNYIYSLKNKKTPSAEHISKIADYFNVSTDYLLGRTDNPT IANKKEQFFFEGKEVDVEELASTAMRFNGKPLTEEDKKAIQNIIEIYLRKQ(SEQ ID NO 1578)>orf02763MTEKEFSQNLGIDIEIFEDGLFPDEAFYIPALKTMFLSDAISDEKRVQVALHEIGHRNHAPDTYQLFRE KCELEANRNMIHHLMKAELDIAEDATTFNYLVFMEKYNLKTIADEIMVKEEYLALLN (SEQ ID NO : 1579)>orf02764MNIIAIIIIVIFVGGVIGAVIDNQKKSPEQRERELETFRANQEKKKQEKKQNIITCPNCKSKDVTFLQQ DKKAFSVGKAVGGAVLTGGVGALAGFAGKKGNKQWHCQNCGNFFETK(SEQ ID NO: 1580)>orf02765MWMEELSNGKYKFFERYKDPYTEKLKKVSVTMEKKTPQARNQAAILLQEKINKKLSTKQVESITFEEIY NLFYKSWAQTVKESTKHNCKSVDKKMKEVIPSDTILANLDRRFLQEAIEKIIESNGYITAKKVRHRLRGIFNYAVQY SYIENNEVDYTTIPQKPKTLEELEKKRNNFLTMQEIKALVDVLNRREYHQKYADMVLVLTLTGMRYGELTALQLKNI DFENNKIEITGNFDSVNKIKTLPKTTNSIRTIKVSESVIEAIQRQIVRLSERFQPLSSDDYIFCFEKWNQPTTIAC FIQILKKYGKQAKIEKNLSSHIFRHSHISFLAESGLPIKSIMDRVGHSNAKMTLEIYSHTTEDMEDKLVNKLDTIF (SEQ ID NO 1581)>orf02777LHPFTRNITCDRYILALFSNLVNFIHVDNPTFCTLNVKVSSLQEFEEDIFHILTYITSLRQSCRIRNRK RYIQALSQGLSKESFP (SEQ ID NO: 1582)>orf02778MIINRHCQGTLGTILTDYIVVQDMEEFDWFWYLRQVCQDFLNQFFSNNFLS(SEQ ID NO : 1583)>orf02786LKTKIGLASICLLGLATSHVAANETEVAKTSQDTTTASSSSEQNQSSNKTQTSAEVQTNAAAHWDGDYY VKDDGSKAQSEWIFDNYYKAWFYINSDGRYSQNEffHGNYYLKSGGYMAQNEfflYDSNYKSffFYLKSDGAYAHQEffQL IGNKffYYFKKffGYMAKSQffQGSYFLNGQGAMMQNEffLYDPAYSAYFYLKSDGTYANQEffQKVGGKffYYFKKffGYMAR NEWQGNYYLTGSGAMATDEVIMDGARYIFAASGELKEKKDLNVGWVHRDGKRYFFNNREEQVGTEHAKKIIDISEHN GRINDWKKVIDENEVDGVIVRLGYSGKEDKELAHNIKELNRLGIPYGVYLYTYAENETDAENDAKQTIELIKKYNMN LSYPIYYDVENWEYVNKSKRAPSDTDTWVKIINKYMDTMKQAGYQNVYVYSYRSLLQTRLKHPDILKHVNWVAAYTN ALEWENPYYSGEKGWQYTSSEYMKGIQGRVDVSVWY (SEQ ID NO : 1584)>orf02791MHKNFVVVVTDFFTAVQFIQFNKEGTTCHNTTKFFNHLDSCLNSSTCRQKVIYNKNTLTWLNGIRVHS QGIDTVLFFIVSRNNFAWQFTWLTNRRKTNSQLKGNWTTHDKSTSFRSHDHVDFLVSSILNDFTNSVAISISISHQ RTNITEGNAFLffIIFNCCNVIF(SEQ ID NO : 1585)>orf02795MEIKEQTRKLAVSYSKYSFEVADKTDEVSNHTYGKATLTWFEEIFEEYKEHHNIDV(SEQ ID NO: 1586)[3606]>orf02801LHKTLENIGEFEEDNLYYSSMTKAETRISFPIFSLILHYI (SEQ ID NO 1587)>orf02803 MLNRQVCFCFVNHISPLNVVIWENLSLEELLYAICICFITHKIAKQTSLTIDNAGIAMNNIR (SEQ ID NO 1588)>orf02808LNSRFFYTDFFKGRQAKGCSFSCTSLSLTDNILAFKGQRNSLFLDRTSFYKTSFFNFC(SEQ ID NO: 1589)>orf02821MRFLADQDRIQHHRYSffALFDKVQGLLSHTDSREKTNLNSPKFHIT (SEQ ID NO : 1590)>orf02822MLKNGIISWKDFKSFFCQGCQTSHCYKPMQAVQGIGSQIS (SEQ ID NO : 1591)>orf02825VTAHRIFGTSSIHNKLIGLAMFGITAMKIICHKLNRNHINIFRRLGIQGKTEFLLIHLIRQVKMNDLSQ GMNPTICPTSTVNSNGLPFI (SEQ ID NO: 1592)>orf02829MLARSKNCFMKSLSIFLLIFYFFDSYQISKKRRSLIGL (SEQ ID NO : 1593)>orf02840LEVCIHHHHQISCRILQACIKGCFFAKISRERNIMDCRILLPIGL(SEQ ID NO : 1594)>orf02847VDRTDEVSSKHCFEVVDRTDEVSNHTHGKATLTWFELDFRRV (SEQ ID NO : 1595)>orf02893MIAEFIDGLQKFHFLQNALITAIVVGIVAGAVGCFIILRGMSLMGDAISHAVLPGVALSFILGLDFFI GAIVFGLLAAIIITYIKGNSIIKSDTAIGITFSSFLALGIILIGVAKSSTDLFHILFGNILAVQDTDMFITMGVGA AILLLIffI FFKQLLITSFDELLAKAMGMPVNFYHYLLMVLLTLVSVTAMQSVGTILIVAMLITPAATAYLYANSL KSMIFLSSTFGATASVLGLFIGYSFNVAAGSSIVLTAASFFLISFFIAPKQRYLKLKNKHLLK (SEQ ID NO 1596)>orf02913MYEEPEVAPVHPTGPTPATETVDSAPGFEAPQESVTIL (SEQ ID NO : 1597)>orf02945MGNNGQFTFGYRHDFFQNQLAIFNALVDTFTRRTIDIKTLNTFINEVLNQGTRTLWTYFSLLIITCVEG WNDTFVFFQI (SEQ ID NO : 1598)>orf02948LTKIFGWILRIAVLAADVYGNFANNIAVAWDAHDKIPNNGRINF(SEQ ID NO : 1599)>orf02974LSTRNKYCKNLIIFESTFNILDIVKKDLKLNSKLEKDLKY (SEQ ID NO : 1600)>orf02976MSYFRNRDIDIERISMNRSVQERKCRYSIRKLSVGAVSMIVGAVVFGTSPVLAQEGASEQPLANETQLS GESSTLTDTEKSQPSSETELSGNKQEQERKDKQEEKIPRDYYARDLENVETVIEKEDVETNASNGQRVDLSSELDKLKKLENATVHMEFKPDAKAPAFYNLFSVSSATKKDEYFTMAVYNNTATLEGRGSDGKQFYGNYNDAPLKVKPGQWNSV TFTVEKPTPELPKGRVRLYVNGVLSRTSLKSGNFIKDMPDVTHVQIGATKRANNTVWGSNLQIRNLTVYNRALTPEE VQKRSQLFKRSDLEKKLPEGAVLTEKTDIFESGRNGKPNKDGIKSYRIPALLKTDKGTLIAGADERRLHSSDWGDIG MVIRRSEDNGKTWGDRVTITNLRDNPKAFDPSIGSPVNIDMVLVQDPETKRIFSIYDMFPEGKGIFGMSSQKEEAYK KIDGKTYQILYREGEKGAYTIRENGTVYTPDGKATDYRVVVDPVKPAYSDK⑶LYKGNQLLGNIYFT TNKTSPFRIA KDSYLWMSYSDDDGKTWSAPQDITPMVKADWMKFLGVGPGTGIVLRNGPHKGRILIPVYTTNNVSHLNGSQSSRVIY SDDHGKTWHAGEAVNDNRQVDGQKIHSSTMNNKRAQNTESTWQLNNGDVKLFMRGLTCDLQVATSKDGGVTWEKDI KRYPQVKDVYVQMSAIHTMHNGKEYIILSNAGGPNRENGMVHLARVEENGELTWLKHNPIQKGEFAYNSLQELGNGE YGILYEHTEKGQNAYTLSFRKFNWEFLSKDLISPTEAKVKRTREMGKGEMGKGVIGLEFDSEVLVNKAPTLQLANGK TATFLTQYDSKTLLFAVDKEDIGQEIIGIAKGSIESMHNLPVNLAGARVPGGVNGSKAAVHEVPEFTGGVNGTEPAV HEIAEYKGSDSLVTLTTKEDYTYKAPLAQQALPETGNKESDLLASLGLTAFFLGLFTLGKKREQ (SEQ ID NO 1601)>orf02978 [3637]VDKTDKVSSKHRFEVADRTDEVSSKHRFEVADRTDEVSSKHRFEVADRTDEVSSKHRFEVADRTDEVSS KHRFEVADRTDEVSSKHRFEVADRTDEVSNIYTARRS(SEQ ID NO: 1602)>orf02989MSCNCAFYRSQFFDVNSVSNYHSHQKELRFPNSILFTYFVKVT (SEQ ID NO : 1603)>orf03007 MTVKHRIVNSNGEARSGESLTTCGTRSTHGNWATVGYVYAADMARQNWWDLSAAISGSWSPN (SEQ ID NO 1604)>orf03009MRWDYGQIFKEIRKSKGLTQQDVCGQVIHRTTLTNIEHGKVIPSFENMVFLLEQIDMSLAEFKYICNEY HPSKRRDIIVESQNPSTFQDTRKMVELTEKCQKYLKTHHDVPIQNIYRHTKIVTELRTKGFKNNHVLKDLYEEIWDY LEPMDTWYISDLKLLGTILFFFPSENLPLLIDRIMKTIEKYKYFRETKAFLSSFLANLSTVYFQHHLFKECETITLQ LLVLAEELKIYDILGFSQVRLGILQHNSDLIDKGITLLRLTKEEALVKILEKEINDFSNL(SEQ ID NO 1605)>orf03014VGLIKLTSYVFVCISNSFLTRHDKNDNICFFHGNFCLVLDLFHERSIDIINSSCINHAKRTIEPLTRCI NTVTCHSFDIFYNGDSLTSDPIK (SEQ ID NO : 1606)>orf03016LSSKSCIDRTNQETFHTLGLEGVGMKSGSLFCSVQISDKEKENSRLANGFLRYQFIQGIFLLLTSYHNH RVGLEILPR (SEQ ID NO : 1607)>orf03049MTESYTWVEADRATLSRYRHGQGHLTDQFFSFKVQRPAAKTLIASISTGKGMGPSFDGTPVITSGNQ NRINTIKNSFIMSSSSVRISLRKLTSQRNFLRNLSSLILLAAQVAKGDATACSHQRISRVVGQDSHETLSLTEFF (SEQ ID NO 1608)>orf03050MNlNNEKVffFAFYLLDMQITRPTPTFNDRRIGLIGKLQELRFLAGNLLLR(SEQ ID NO : 1609)>orf03051LIKGYLPNHLALMDLCSKTTCTLDDFAGIAGRRNHRGFFCHIGNGVFLTVDKYLRNQRIRQRKSSHHILTQLVCHSHTHLFILLQTSLSLRTKERLSF (SEQ ID NO 1610)>orf03057LIKLTDRNFSDILIKCLIKCFTNLLSNQLMLLPSTLKL (SEQ ID NO : 1611)>orf03060LFKGGVTISRTPLSSEDTVMIDATEVQINCPKKTISE (SEQ ID NO : 1612)>orf03062MIQSENHCSASHSNRDYQSQHDNQGRTCQCFIIVPCHKKGSCSVGEITWNQRCQNGQDKDHSRCLIKNT (SEQ ID NO 1613)>orf03069miarqlmvffstnqadtri msidsliinnskdfqssshasvsfiltklvnllifnf(seq ID NO:
1614)>orf03070MGEPFTHFIDCIDLGINPSYTQVCDRHFTSDIPCTMTSHPIS (SEQ ID NO 1615)>orf03077LSSDSHFIGIKAFVILILGKSNSIVLRIVGLYQDLTCFFSPTCSTCHLSQELEGSLRRTEIRQIQGRIR I (SEQ ID NO : 1616)>orf03078MAVHSLGIHMQGQRNIAVGTSIHRPTLPTHDKARITTAIEHENHLLFFNQTVLDSL(SEQ ID NO:
1617)>orf03079MVTGIAVLLISHFMLFINNHDTQIFQRSKDSRSGTNNNLGIATLHLAPFIILFTIG(SEQ ID NO:
1618)>orf03080VKNGYLVPKTCYKTLGHLRSQGNLRYQQNSCLALIQGTLDNLQVNLGLPTSCNPLK(SEQ ID NO: 1619)>orf03081MVNLIPRLGLDLLLIDCLIFQTKQAFSSQTHHFSLLGKV (SEQ ID NO : 1620)>orf03082LGLQTKNNPLNQAIPLTKRHMNPHPNFQHSLKFLRNPVTIGLVRLHQGHIYDNLS(SEQ ID NO: 1621)>orf03085LGNHFCTICSTTYQAILQFIQIffffCQEDKDSIWNLFLDLKSTLNFNFKENIDSLVQGFIDIGQRSSIVV ADIFCVFQHLSLTNQLFKFFTSTEEIVNTVHFSRTLCACRHRYRILKLVFRTLKNLSSNRSFSNP (SEQ ID NO 1622)>orf03092MKFKNYLFDLYPYFPKGFSLDNREDPDVCSKALYDDLCKMFFDDDSKEKLKITSVCNKCQNYGNRDYYT LFIDKDKYLLSSDYIGASIYffAQEAGLNDRIILDHLSISRTIGGHILFPRGGKLETVNQARGGEKGYYDRFDLTLYA IKEWFVENKNTKIGYAIENYHEWFELFSGDDNCKNGFENFVEFFKLEGFIYEQNKIIDLIKSDLENNQVVFLDKEDI LIASTEEEYIRYMKNLNIIILERTKKILL (SEQ ID NO : 1623)[3680]>orf03093MELSIQLIHDLNTHTTHSTAKMLHNVKAIKNDFSIRE (SEQ ID NO 1624)>orf03096LKAKLFSQVIVRAKHIHSNNFDATSDSSIVAKKVISNDSLFSSLKNSDDIEIVKILRNEAHLSLCKSIL IPRHNLRKTRKIMFKVKIKEQTRKLAAGCT (SEQ ID NO: 1625)>orf03113VGCSYICHELVANHDHFLFVIVEFLHGTVNTKCEGLQGPVNVINPKFLNCSLNAFFGVI(SEQ ID NO 1626)>orf03114 [3687]LLHLWRSIRVVPSNEGIIQIDQNSLDSLRLQAffDCQIIDCFHSKIffYIIFNRHSGSFS(SEQ ID NO: 1627)>orf03118VKGLLLATKLCRTNSHTDNLTRYSNRSICQNDLISHIQLTFKEDEKAIDDIRQKALGSHTNRYPSNTSS SQQTRNWQT (SEQ ID NO : 1628)>orf03120 LWGILGLTLPNLSGIGLL ⑶ LFVGGLKAVAPILVFALVANALSQHQKGQDSNMKTWFLYIL (SEQ ID NO 1629)>orf03121MIGTFAAALVAVLASFIVPIEITLNSANTEIAPPDGIGQVLSNLLLKLVDSPVNALLTANYIGILSWA VIFGIAMREASKNSKELLKTIADVTSKIVEffIINLTPFGILGLVFKTISDKGVGSLANYGILLVLLVTTMLFVAPV VNPLIAFFFMRRNPYPLVWNCLRVSGVTAFFTRSSAANIPVNMKLCHDLGLNPDTYSVSIPLGSTINMAGVAITI NLLTLVTVNTLGIPVDFATAFVLSVVAAISACGASGIAGGSLLLIPVACSLFGISNDIAIQIVGVGFVIGVIQDS CETALNSSTDVLFTAVAEYAATRKK (SEQ ID NO: 1630)>orf03124MKIKEQTRKLAAGCSKHGFEVVDRTDEVSSKHRFEVVDRTDEVSSKHRFEVVDRTDEVSSKHCFEVVDR TDEVSSKHCFEVVDRTDEVSSKHGFEVVDRTDEVSSKHGFEVVDRTDEVSSKHSFEVVDRTDEVSSKHGFEVVDRTD EVSSKHGFEVVDRTDEVSSKHGFEVVDRTDEVSSKHSFEVVDRTDEVSNIYTAR (SEQ ID NO : 1631)>orf03145MKDLISVIVPVYNVEPFISSCLDSLSKQIYQNFEVLLVNDGSTDNSGAICREYADRDSRFHYFEKENA GVADARNFGIERSK⑶YITFVDSDDWVTEEYLSILIETLKEQHSEIWSTYSTYNESDGLFYIHVFDSDYYVKNYN SKLLMEELPLLERYDMSFLTSWGILFKRELFQEVQFPFGRVCEYIGTNYKLFMQVEKVTYINKVLYWYRVGKEGLSN SYSPKMMRDDCDFRLERIAVLALKGYDVSKYLDQMKFYLKYRHDIAIQRELKENVETRHLEMLDYLLNGNKYN(SEQ ID NO 1632)>orf03148LNVRGGAYITFVDSDDWLEHDALDRLYGALKKENADISIGRYNSYDETRYVYMTYVTDPDDSLEVIEGK AIMDREGVEEVRNGNWTVAVLKLFKRELLQDLPFPIGKIAEDTYWTWKVLLRASRIVYLNRCVYWYRVGLSDTLSNT WSEKRMYDEIGAREEKIAILASSDYDLTNHILIYKNRLQRVIAKLEEQ匪QFTEIYRRMMEKLSLLP (SEQ ID NO 1633)>orf03167[3701] VLAKAEAEALVDADSDADVLADTEAEALVDAEAEALVEADAEALVLAEAEALVDAEADALVEAEAEALV DADADALVDADSEALVDADSDALVLAEAEALVDADSEALVLADSDALVLAEAEALVDAEADALVDAEADALVLAEAE ALVDADSEALVDAETEALVDAEAEALVDAEADALVDADSDALVDADSDAEVLAEADALVDAETEALVEADSDAEVLA EADALVLAEAEALVDAEADALVDAETEALVEADSDAEVLAEADALVEADSEAEVLAEAEALVDADSDAEVLAEADAL VDADSEALVDAEAEALVDAEADALVLAEAEALVDAEAEALVDAEAEALVLAEADALVDAEADALVDAEAEALVDAEA EALVDADSDALVDADSDAEVLAEADALVDADSEALVDAEAEALVDAEADALVLAEADVLALVDADSEADVLAEADAL VDAEADALVDAEAEADVDADSDAEVLAEADALVEAEALVLAEAEALVDAETDALVDAEAEALVDAEADALVLAEADV LALVDADSEADVLAEADALVDAEADALVDAEADALVDAEADALVLAEADALVLAEADALVLAEADALVLAEADALVD ADSEADVLAEADALVDAEADALVDAEAEALVLAEAEALVLAEADALVDAEADALVLAEADALVDAEAEALVLAEAEA LVLAEADALVDAEADALVLADSDALVDAEADALVDAEADALVLAEADALVDADSEALVDAEADALVDAEAEALVLAE AEALVLAEAEALVDAEADALVDADSDALVDAEAEALVLAEALVLAEADALVDAEADALVLAEADALVDAEADALVLA EAEADVDADSEADVLAEAEALVDAEAEALVLAEAEALVNAEADVLAEADALVDADSEALVLAEADALVLAEAEALVD AEAEALVDAEADALVLAEADALVLAEAEADVDADSDALVLAEAEALVDAETEALVDAEAEALVLAEAEALVLAEAEA LVDAEADALVLAEADALVDADSEALVDAETEALVDAEAEALVLAEAEALVLAEADALVDAEADALVDAEAEALVDAE ADALVLAEADALVDAEAEALVDAEADALVLAEAEALVDADSDALVDAEADALVDAEAEALVDADSDADVLADTEAEA LVDAEADALVLVDADVLALVDADVLADVLALVDADVLAEAEALVLAEAEALVDAEAEALVDADSDAEVLAEADALVL AEADALVDAEAEALVDAEAEALVDAEAEALVDADSDADVLAEADALVDAEADALVLAEADALVLAEADALVDADSEA LVDAEAEALVDAEAEALVDAEAEALVDAEAEALVDAEAEADVDAEAEALVDADAEALVLAEADALVDADSDADVLAE AEALVDAEADALIDADSEADVLAEAEALVDAEADALVDAEAEALVLADAEALVDAEADALVDAEADALVDAEADALV DAEAEALVDAEADALVLAEAEALVDAEADALVDADSDAEVLVLAEAEALVDAEADALVDADSDAEILAEADALVDAE AEALVLADSDALVNAEADVLAEADALVDADSEALVLAEADALVLAEAEALVDAEAEALVDAEADALVLAEADALVLA EAEADVDADSDALVLAEAEALVDAETEALVDAEAEALVLAEAEALVLAEAEALVDAEADALVLAEADALVDADSEAL VDAETEALVDAEAEALVLAEADALVDAEAEALVDADSDADVLADTEAEALVDAEADALVLVDADVLALVDADVLADV LALVDADVLAEAEALVLAEAEALVDAEAEALVDADSDAEVLAEADALVLAEADALVDAEAEALVDAEAEALVDAEAE ALVDADSDADVLAEADALVDAEADALVLAEADALVLAEADALVDADSEALVDAEAEALVDAEAEALVDAEAEALVDA EAEALVDAEAEADVDAEAEALVDADAEALVLAEADALVDADSDADVLAEAEALVDAEADALIDADSEADVLAEAEAL VDAEADALVDAEAEALVLADAEALVDAEADALVDAEADALVDAEADALVDAEAEALVDAEADALVLAEAEALVDAEA DALVDADSDAEVLVLAEAEALVDAEADALVDADSDAEILAEADALVDAEAEALVLADSDALVNAEADVLAEADALVD ADSEALVLAEADALVLAEAEALVDAEAEALVDAEADALVLAEADALVLAEAEADVDADSDALVLAEAEALVDAEADA LVLAEADALVDADSEALVDAETEALVDAEAEALVLAEAEALVLAEADALVDAEADALVDAEAEALVDAEADALVLAE ADALVDAEAEALVDAEADALVLAEAEALVDADSDALVDAEADALVDAEAEALVDADSDADVLADTEAEALVDAEADA LVLVDADVLALVDADVLADVLALVDADVLAEAEALVLAEAEALVDAEAEALVDADSDAEVLAEADALVLAEADALVD AEAEALVDAEAEALVDAEAEALVDADSDADVLAEADALVDAEADALVLAEADALVLAEADALVDADSEALVDAEAEA LVDAEAEALVDAEAEALVDAEAEALVDAEAEADVDAEAEALVDADAEALVLAEADALVDADSDADVLAEAEALVDAE ADALIDADSEADVLAEAEALVDAEADALVDAEAEALVLADAEALVDAEADALVDAEADALVDAEADALVDAEAEALV DAEADALVLAEAEALVDAEADALVDADSDAEVLVLAEAEALVDAEADALVDADSDAEILAEADALVDAEAEALVLAD SDALVDADSEALVDAETEALVDAEADALVLAEAEALVDAEAEALVLAEAEALVLAEADALVDAEAEALVDAEADALV
LAEAEALVDADSDALVDAEADALVDAEAEALVDADSDADVLADTEAEALVDAEADALVLVDADVLALVDADVLADVL ALVDADVLAEAEALVLAEAEALVDAEAEALVDADSDAEVLAEADALVLAEADALVDAEAEALVDAEAEALVDAEAEALVDADSDADVLAEADALVDAEADALVLAEADALVLAEADALVDADSEALVDAEAEALVDAEAEALVDAEAEALVDA EAEALVDAEAEADVDAEAEALVDADAEALVLAEADALVDADSDADVLAEAEALVDAEADALIDADSEADVLAEAEAL VDAEADALVDAEAEALVLADAEALVDAEADALVDAEADALVDAEADALVDAEAEALVDAEADALVLAEAEALVDAEA DALVDADSDAEVLVLAEAEALVDAEADALVDADSDAEILAEADALVDAEAEALVLADSDALVDADSEALVDAETEAL VDAEADALVLAEAEALVDAEADALVDAEAEALVDADSDAEILAEADALVDAEAEALVDADSDAEILAEAEALVLAEV DALVEADSDADVLALVDADVLALVDADVLADVLVLVDADVLAEAEALVLAEADALVDAEAEALVDADSDAEVLAEAD ADALVDAEAEALVLADAEALVDAEAEALVDAEADALVDAEADALVDAEAEALVLADAEALVDAEAEALVLAEADALV DADSDALVEADSDAEVLAEAEALVDAEADALVDAEAEALVLAEAEADVDADSEADVLAEADALVDAEAEALVLAEAD ALVDAEADALVDAEADALVDAEAEALVLAEAEALVLAEADALVDAEADALVLADSDALVDAEADALVDAEADALVLA EADALVDADSEALVDAEADVLVDAEAEALVLAEAEALVLAEAEALVDAEADALVDADSDALVDAEAEALVLAEALVL AEADALVDAEADALVLAEAEALVDADSDAEVLAEAEALVDAEADALVDAEADALVLAEAEALVDAEADALVLADSDA LVDAEAEALVDAEADALVLAETDALVDADSDAEVLAEAEALVDADVLADVLALVDADVLADVLALVDADVLADVLAL VDADVLADVLALVDADVLAEVDALVDADVLADVLAEADALVDADSDAEAL (SEQ ID NO : 1634) [3702]>orf03175VFEVVDKTDEVSSKHCFEVADRTDEVSLKHCFEVADRTDEVSLKHCFEVADRTDEVSNHTYDKVKLTWF EEIFEEYHTKKPCSSR (SEQ ID NO: 1635)>orf03178MYQDLLRKIAEEKPNYNQEEIQWLLDHLGDPSPEIRDDLVFTSFARGIQEELFTQEQFHFIAEGVSSDG GLDKEIDKIGLPTLERSFRALIYATLLSDDANQQSIFYQRLKAEIRNVLLNQGLHYLSKEKDTTGFSSQYGWVHSFA HGADLLKEVVCHPDFPKNRVHEVFDILGQLFKRMSIRFTDDEDffRLARVIYEPILQGKLEQEQVASffIKTVDFPIEE REDFSKFSNFRSCLVEVYVQLDQRNSLQDELKEAIQSFQY (SEQ ID NO: 1636)>orf03181MGFKVSHFKIPSSHLSINVLRTIENFTEIGQGLLHISP (SEQ ID NO : 1637)>orf03182VGFFDFGLTNSCRQVRQFTQTVQDFLVCYHQGIVKEGQGYAGICFKFHPSLGNIGKFVIAIVRRLRHKS IVANMAHLNVDLFQFRKGLLEILKSVKIALVITAKLVDVFTSFLDCTQEILTVLV(SEQ ID NO 1638)>orf03190 MNITYIVGNGLDLQYGLKTRYRDFYEFQNKVYISRTENEEKYSNFIYESLFSDKVNDYENWSDFELSIG
KLTKDNDLISSSIEIKEKFIDDFSEVVDDLREYLRIQQEKNLEKGNAIDFISTLDDMRTSLPVINQPAIDKKYNENP
HQDDIVNIVTLNYTHVIDKLYNGSAKSFRNQLRANLYNFYIEPPIHAHGTVDVCTVLGVSDEIQISNSLEEQKESLI
KSLVLKNYRENMDVKNSDIIKNSDIIILYGVSLGETDRYIWSQIAERSISGSVPVIIYHYVPHFDPGNPIRAKRLYR
NVEDKFIQNSGIDLELEKKLRDNLIVVIGKTIFDLIER (SEQ ID NO : 1639) >orf03191 MNTLLTLRGKSFTQKSRNNGMGPITIPKKTIITLEHLKYLHFSLEETKTYffEKNNIIDGILISIYYNRI
VAKSNRINGYFNVGGGNPFPNDTIVGAKFNDEKTKHIVTHYISRDALNKTITVLSKIIEVFEEHFDRAITCEMFSDS
STFASINFSEYGISKSKFQQYLRDSCFIENFGVEHTTVSDIQNSIVTFYDVHTDIFRLLNKLNIDISEANIMNQTTV
LLDEKNIELLLSKAPYLVSMIVEDFSKLSVDDFSLDNNDLKINLPSPMNEPVVGVIDTLFDKRVYFNEWVEYHDFVS
PDISKDSQDYKHGTAVTSLIVDGANLNPNLDDGCGNFRVRHFGVSLQSGFNSFTIIKQIKEIVSQNADIKVWNLSLG
SNDEIRENFISAEGALLDEIQFENDVIFIIAGTNASVINGKRKRIGAPADSLNSIIVNSVDFNNQSVSYSREGIVLS
FFVKPDVSYYGGGNGDFINVCEPLGLGRVAGTSFAAPFIARKMAYLIHIMGLSREEAKALLIDAAIPffNDKKTFTDLSLIGNGIVPIKMDDILSTPDDEIKFIVSDISRAYDTYNYDFPVPISSESYPYVAKATMCYFPNCSRKQGVDYTNTE MQLTFGRLKSDGIKSINKDNQHAEDTPGYVRENAARNIFRKWDNVKHIGESFTSRKRAKAILNPSNPQWGMSIKTI ERLKS⑶GQGVRFGVWTLKELNGVNRIEDFIQQAELRGWLVNRLQVEAQVDLFNSLNEEIEFE (SEQ ID NO 1640)>orf03192 MKKSDVLDLIKYHYEGRETEFRNQSIAIARNFNKHGDTQIAQYIMGLMSQSDRFMPQIENPSEYLTPAK LDIGPLPLPLSIMNDLKGIINAVNHHIGINKFLFVGSPGTGKTESVKQVARLIGKELLVVDFSHLVDSKLGQTVKNL ATLFNEINNLPFKQNYIILFDEIDSIVLDRVNQNDLREMGRVTSAFLKELDRLSPEIVLIATTNLFENLDKAVTRRF DAIIDFDRYTDEDKVEVATIILNELLKQFKNVARDLKLFKKIINSANVIPNPGDLRNSIRTSLAFSDPSDPHDYQKR LLRSLHNGRNLSISKLSKLGFTVREIEILTGISKSSVSRELSED(SEQ ID NO: 1641)>orf03200MINSQVFEIRIFNSYYKDAIYYFKNINYSIFHIFSTHY (SEQ ID NO : 1642)>orf03205VGHRFDPCRGHLNTTGKALEPRFFCLNKIFFKFFRKLA (SEQ ID NO : 1643)>orf03206MGWKGTPPCLHPSNQDTTILIVQQCLRRIEVLAMINFLN (SEQ ID NO : 1644)>orf03207VFGSYYRVIASIFFKEFWITEISSNQLIWQVCSSYNWILGNLFKVNPVI(SEQ ID NO: 1645)>orf03208VLPSHQVLTFSMSPVHRSPNTIIffIELIKEMVFSTKINKSIffIIDPTNLS(SEQ ID NO : 1646)>orf03219LLRFAIHSNLLFLKRFIFSIKDSAWRCLFISFFETFHFCFKNKSFYLNSFYH(SEQ ID NO : 1647)>orf03230LIVSLKTKSRKAKDMAESIQGWLAQFLVNLFKSITFDCGKEFSKWKDISNHHDSESFFANLECPRQRCL NEHSNRLLRCHDLPKQTDFNEVSQEF (SEQ ID NO: 1648)>orf03231VVEIIYFLIIIIASGLGSISGMGGGIIIKPLMDSFGYHSVSDIAFYSSFSVFIMAIISTTKRFSQSKEI KWRLIFTVSFSSVLGGFLGHLIFQVLLSQLSVRLVSIVQMILLFVMLLVSFVLTDFKKTYQFDKIGFYMICGLLLGL ISSFLGIGGGPLNVSLLMVFFSISIKEATMYSLAIIFFSQLSHLATIVVVTGLNQYHLAPVPVIFLASICGGVLGTV VSKVLPENWVRYCFKGMLFFVMGMTLYNLFHIL (SEQ ID NO : 1649)>orf03232MMGTNSEEGFLDDFEGPQVAVSVKDFSIADTPVTNQEFAQFVKETGYKTLAERQEWSFVFILFVPEAER EGYPHPAGAPffffLQVSNACWKHPYGENSNLVGLEDHPVVHVALEDALAFCNWSGMSLPTEAQWEYAARGGRQSEYPff GDTLLEGGYYHANTWQGRFPYENTALDGFIGTAPVYEFLPNDFGLYQMIGNVWEWCRNPRYTLLASFNEDDYELPKY GIQDEEYAIRGGSFLCHCSYCNRYRVAARNGCISTSTSSHLGFRCLKE (SEQ ID NO: 165)>orf03235MVQTKQPNIILIVVDQMRADALSLNSKDKLVSTPTLDMMASVGYNFENAYSPVPSCVPARAALLTGLD QDKSGRVGYQDEVPWNFTNTLPKVFKDMGYQTECIGKMHVFPSRQRLGFDHVLLHDGYLHVDRKYDKAYGSQFDYA SDYLAFLKGKVGYDVDLI DDGMDCNSWEARPWDKDEKLHPTNWVVSESISFLQRRDPTVPFFLKMSFEKPHAPLNPpkyyfdiymerlpqfldlhignwevlekqipsiyalrgklkeddqrrmvaayfglithidhqisrfltalkefrhdk dtiiwfvsdhgdqlgehylfrkgypyqgsihipsfiydpagliagnrgtikqlvkiqdifpslvdlaggtttdeldg rsvknllfgqyegwrtefhgehalgkdssqyiltdqwkfiwfpvlnhyqlfdmkkdphemndlypsekyqpivrqmk kklvdflryreegfwdeelvpvelskitptltktcdsqs (seq id no : 1651)>orf03237mntmldkmqeklspiamkvgnqkflvalrdsfvgtmpvimtgsialllnaflvdlpqqfhlesitktf qwlvdinnlvfkgsipivsllfiyclgvniakiykvdtvsaglvslasfvisigstvtksfplanv⑶vkldqilq gidnlafdgknlmvtignvipgnhinargyftammigflasiifckvmkknwviklpdsvppaiakpftsiipgfma myivailtyvfhllsndllidwvykvlqtpllglsqsffavilmiflnklfwffglhggnvlapimeglfgvamlan ldafqkgepipyiwtsgsfgafvwfgglglvlailifsrnshyrkvaklglapvlfnigepvnyglpvvlnpllfi pfvlspvfmatvaywatswglvspvtqnvtffvmppilygffstafdffraiilsvvcliisvltyfpfvkmadkte ls (seq id no 1652)>orf03238mnesnlesamglimyggeaksnameaiqaakk⑶fskanrrladanaallqahkaqtemltreaqgeet sisllmvhaqdhlmtsltfvdlakevvevyerfekn(seq id no: 1653)>orf03239makvtimlacaagmstsllvtkmqkaaedkgldaeifavpapeaeeivatkevnvlllgpqvryllcidf qeklkdrqipvavipmtdygmmngskvldlaeslld(seq id no: 1654)>orf03240MKRLISANPSEILQMNAEELKQSI LASEGRVVLSENWTRETFViiD ITNSEIARAFGADMILLNCVDV fepkiyaldssgddvihrlhqlvacpigvnlepidpsakmleetqeivagrvasvetlkrieelgfdfvcltgnpg
tgvsnreiikavqtakenfsgliiagkmhgagvnepvaelsvaeqlleagadvilvpavgtvpafhdqelrevvd
lvhskgglvlsaigtsqetsdtdtikeialrnkicgvdiqhigdagygglatvdniyalskairgvrhtvsrlar svnr(seq id no 1655)>orf03241MEKLLQEKLLPVAARLGNNKALVSIRDGITLTIPLLLIGSLLMVIASFPIPGWEQYL⑶IGVADYLWKG vdssfgllglvasfgiayfmarqykvdgipagivslssfitvtpfirgeagagmptafmaskglfvamilglingyi yqwfinhniqikmpdgvppavsksfsaiipgavtivgwlivyatldklslpnlheiaqvalggplgllgnnviglli liflnssfwfvglhggnvvnavmkplwlanldankvayqtgetlpniftsvfmdnfvfiggggatiglvlalgylah kkkaskqlktlapitvipglfninepamfgvpivlnilllvpfilapmfnllvawgamasglvpltytdpgwtmppv isgllatgsisgsllqivlivldvllylpfviaiekrfklled(seq id no : 1656)>orf03242MTLSKKQLQLRAKILETVYTLGPISRIEIATKTGITPATTSSITNDLIKENILLELGEDEHDTSVGRKK illdiqakrfyyigcelsekhftfal⑶nlgnilkeekeivtkqliqekgnqlinqtlkqflnncsdyeieaigial pgrylddykittnnplwqhidlemiqshfdkplffsnnvncmaigkrlfsrqqndpnfayfhfargmhcsyiydgni ygkgnlmigeightvvssegeecscgrkgclqtfageswlikkskilyhqspysllpslvknaddidiqviltayql gdtgiitlihqallylsqtilnismmidsqkiylhsplltnqhiiqklysemnykpkllynrlpeviiepyndftaa hsaialclyhtilhs (seq id no: 1657)>orf03243[3748]MTIRFEEKVSTENAQFVCQWSNSLGKVFQEQWIGPRIPFPLTIQVFQDLEGILSIFEGQEFVGLIQKI RLEDSNLHIGRFFINPQKQGQGLGSQALRKFVSLAFENRDIDSISLNVFEANQRAQNLYQKEGFEIV (SEQ ID NO 1658)[3749]>orf03261MPFKENLICQHRNHHCSVFFISLGLLHNIHIEIDISQTRASFLDLSDYLQAVLMILQKFCQAIGLAQRL DLLQLHLLHLTRLLL (SEQ ID NO: 1659)>orf03271MYLLLLVVKDHIALIDKEMHVWRPNCILRDLTNFFIKRNHIVTHKTNGSTTKR(SEQ ID NO : 1660)>orf03272VLTLMNHFIKEIQGIPINHLTILIENSIFKLNLKNWIIG (SEQ ID NO : 1661)>orf03274VDRTDEVSSKHCFEVADRTDEVSNHTYDKATLTRFEEFFEEYKGVPR(SEQ ID NO : 1662)>orf03293VCQRMDARTCKTTIIAVHNVLTALQQTffIAVQLYQTK (SEQ ID NO : 1663)>orf03294LHLGKSILSLPVKGKDLEFLVHLFVINHWIGFPSRTSTFCRCKVLNSME(SEQ ID NO : 1664)>orf03295LEQTVIIANNPCELYWDNHLSFLSDSLLKQVIVHLKRICLDIHHDRGCSHVRNDTT(SEQ ID NO:
1665)>orf03297LTDDGVLILVVDAGWRGNSCLQEQGCHHFRAILLCITWHFRSCTDKGHLTFKDIDQLRQFVQTDTSDEI SNLGNTAIVSRSHQTSFFIRIRHHGTELPNLEPTVVLGHTLLLVNHWPLAIQLDPNAQDEKDGRS (SEQ ID NO
1666)>orf03298MLKMRKMGEVRTSKTKAKTQSKQRLKISEPFLLETSff (SEQ ID NO : 1667)>orf03313MLEEGTKDQLAELTYPFGRGVNLSFGIKDVPKLYQKVMEANYPIYRLLTKRKFRVSDPYIYPHKFAVLD PDGYFLRFSE (SEQ ID NO : 1668)>orf03316MDQNLFNYNDEDIDSVIEYSHKLLNRKFSDVMEEYNRSLYKSYDDYNDRVVSEVQDKAISMKSKGQYGN YIEKYFYGYQPNSDSEADFEKIGVELKVTPFKINKNGTLSAKERLVLTILNYMEENLEDFYSTHLWKKCAKILLLFY NGLIPNQTMKDYVIEKIFLYEWFEEDMAVILEDYQKITDKIKNGKAHELSESDGNYLSTCTKGAGKGKDLRQQPFSH ELAKQRAWELKSSYMTYLINHKIFNQSDQESVLANFRGEKKSFTEVIAEKILSYKGFSEQELYDRFEVNSKAKGKNS TLIRKILGLTCDLDKTKEFQKANMNLRVIRVDKNNLPKEDSPFKTYCFKELAATDSWESSHVYNEIYNKRFLFVIFK EIEPKLFVLDSIKFWGFQDRQLEEIQRVWQETRQIISDGVKLTQNGNKVSTNFPQSKINKILFTKLHATNTYYEIDK GKFVGKGSLSDTDELPDGRRITKHSFWMPKKFIKEILDGNWD(SEQ ID NO : 1669)>orf03317MKVLELFAGVGGFRIGLENADKQLFKTKWANQWEPSRKSQDAFEVYDYHFPNSKNINISISDITDEQFS KMDADMIVGGFPCQDYSVARSKKNEKGIEGKKGVLFffEIIRATEIIKPKYLILENVDRLLKAPSKQRGRDFAIMLTAFNNLGYSVEWRVINAAEYGRSQRRRRVFFFVYRNDTVFAQKIDNLYEKNEEIFEDNRYDDYIFNQGLFAKQFPIKPI AVKNRHVFYELPNDIVEVSDTFTGTVffNTGIMRRGKYYSIDTEPNYNGNPITLGEILQDESEVPEKYFLTDQSKLEK FQYLRGPKKIERTSSDGHQYIYSEGGMSPYDDLNLPGRTMLTSEGTVNRSTHLLFVNNKYRLITPIEAERLQDFPDD WTAKKKLSDDSIVEVSDKMRMFFMGNALVTEIVKEIAKFIKEID (SEQ ID NO : 1670)>orf03318 MDTFSFNGQYIVEFSCLKVVDRGLECHPIKSQRDNHQTTDLVT (SEQ ID NO : 1671)>orf03320MGIAIVVERRVHYFGRHHNVTISHFFNFVIFKGRYSVKMKVFHRFLLIFQTTL(SEQ ID NO : 1672)>orf03333MIACRHDICKSQKGLEHPFCIIRRLTRDFNQRPVCIVEANIFCLKITPQIIT匪IVARTVKSSKTGITL TTSMCKRDNHKITWFHRRNGFPSFFNNPNRFVSTIFMSSFRFWITVPP(SEQ ID NO 1673)>orf03341MLRQFRLGFFDVRMTECHLKffKERENFHDFLKFYCKDS (SEQ ID NO : 1674)>orf03350MNMNKDQIAILNGADNLNLTLWMTLKEICKEGCKSFFPVRNTCRMLDIGIPYRLGLSLSNSSVLNGMDV (SEQ ID NO 1675)>orf03370MHKLRIFVNQLCRRFGIILGPFLVLGFQVLTQELELAIFFDLREEVLLQVIPQVCHFCYLRKEFTTLNQ HELTSHDHVLTRHFQTHGLQG (SEQ ID NO: 1676)>orf03382MLHMNLFFQPFFTNLCKTLATGCCVKTVMEWSSIATTIDFKIIE(SEQ ID NO : 1677)>orf03383LDNRAKEffIMSTAQNQAI HLSNQGTQGFIDHLLGNTG (SEQ ID NO : 1678)>orf03385LSLDFFPDDRSRSVTSNDNHFDILGQEKVDQLPSIFTNLLSRTGAIGRPRRISNIDDFFMGKLAHELAH NGQAPDTRIQKTNWSIIHTVFFLVFFLIDRSL (SEQ ID NO: 1679)>orf03394VSYGSHIFFASNCLKQIFGFLFKFSHLILLILVKASLI (SEQ ID NO : 1680)>orf03397MTSLLTLENIHKTFEAGTVNENHVLKGLDLEVEEGDFISVIGGNGAGKSTLMNILAGNLSVDE⑶LLLA GKSIKNLSVRKRAKDIARVFQDPKMGTASRLTIEENMAIALRRGQKRGLGWGVKEKDRIQFQEALKELNIGLENRLK VDTQYLSGGQRQALTLVMTDLMKPKLLLLDEHTAALDPKTSQMVMDLTQKIVEHHQWTTLMITHDMNHAIEYGNRLI MLYQGKIVVDVKGEEKKHLTVEDLMHLFQKNSGQSLVSDELVLG (SEQ ID NO : 1681)>orf03398MNFVLSSLSEGLLWSIVAIGDYLTFRILDIADMTAEGAFPLGAAVVVSQIQAGANPWLATLLALLAGM VAGLVSGMLHTKMKIPALLTGIVTLTGLYSINIKIMGSVPNLSL⑶SATVFKQLASLGLTNEGAVFSLSLVCFLLV CLVLTLLMKTEIGLVLRSTCDNIPMSEANGVNVDTMKIVGYMISNGLIALCGSLFAQNDGFSDVTSGTGTIVVGL S SVIIAEVLIHDLTIGGRLLSIGIGAIVYRLIILNIYEIPNLDQNLVRLFNAILLALVLFAPELQKRLKIRGLKL RNE(SEQ ID NO 1682)[3797]>orf03399MAEVDMVFVPTDNIILSTMETVKQVSIKHKVPVFGGSTEMIAVGGLYNYGTNYEELGRQTARMLIRVLK GEEPENIAVELPEKLELHTNQEMADALGIDISKLEGKE(SEQ ID NO: 1683) [3799]>orf03400VDELAKQGYVEGENIEIDLQNAQGEQRNLKTISQQLAESSDVVLAIARPSAQSLANTTQTTPVIFSAVT DPVSAKLVESREHPGGNVTGTSDQSSDAISTQINLIKKVLLKAKTIGILYTQSEPNSVV (SEQ ID NO: 1684)>orf03401MQTDQRSQEEPHYQEGASDFRTTFIMKLLLRKDKTKNRLDTI (SEQ ID NO : 1685)>orf03402MLPILSPFSSPVNNISEFFKIFRKFFQEAFKVFQISPTKKVL (SEQ ID NO : 1686)>orf03412MINVNQVSIEVKNTFKNWNFTSSIELTTFSKFSQSPTMT (SEQ ID NO : 1687)>orf03414LIDVLFINSFIGRICFYCYRRIHATCLFLQLFSIVILNVAHTLKHSIFIVITFISRCRNFIIVRILLEN QFSRNQGIDNRVGQSRY (SEQ ID NO: 1688)>orf03423MKIKEQTRKLAAGCSKHCFEVVDETDEVSNHTYGKVKLTWFEEIFEEYKKSSWNL(SEQ ID NO: 1689)>orf03442LVEQLTFNQWVTGSSPVRVIYAGLAELADAPDLGSGA (SEQ ID NO : 1690)>orf03443MSIVKSHSFSISLGIFNSFffNNIHTSECFNFLCKGKSNRSNSTISVNQMVFFINIQRFYCFAIEDFCLL RI (SEQ ID NO : 1691)>orf03444LNTLLPPDNLCLFTIYLTGFSCICINSYCHNFWEIFNQLFYQLS(SEQ ID NO : 1692)>orf03451MGFSMKLIHDLNTHTTHSTAKMLHNVKAIKNDFSIRE (SEQ ID NO : 1693)>orf03460MYNKVILIGRLTSTPELHKTNNDKSVARATIAVNRRYKDQNGEREVDFVNMVLffGRLAETLASYATKG SLISVDGELRTRRFEKNGQMNYVTEVLVTGFQLLESRAQRAMRENNAGQDLADLVLEEEELPF (SEQ ID NO 1694)>orf03464MQFTRTAHHTKTLFTTKFTWENEIPFWHHSSRKRDNGFQPHTRIGSSCNDLYSLITCDCNLADVEWTI WMGYHLNNFTDNKLRFLIINNFFCKTFRLQLLVQTSDLLICQKDLTALCSFK (SEQ ID NO: 1695)>orf03469MILDSFFAFNCSGTMKVSTWVYDKGEWYYVSSSGSMIANDffVKDNGK(SEQ ID NO : 1696)>orf03476MCTSINKKKKAVKPSFDLFFCFIFCKLTIVQVSVEATLRHQFLIVALLDDISIFHDQDQVCISDG (SEQ ID NO 1697)[3827]>orf03484LHLRTCFVRQTNKLSPLINRTRLQFHQTILHYTLNQITSNRLGNIEFLIDIFNQDQVLVFLAIIQKMHNLTLRPTHKFNAATFGFLLHHQVNLMTKTLKD (SEQ ID NO: 1698)>orf03499MLEIWKYRPFVSEFWNDFKNNHDKQFVDSISLYLTLKDDDDPRIEEESEALENMILQYLGEDDAS (SEQ ID NO 1699)>orf03507MAFNQFNRCIGLSIPTAPNVPGTIINRSYLHDATVPNNVREKT (SEQ ID NO : 1700)>orf03523LTDFHDFKFI FFENLFKSRQLYLQSQNTVLSNLffLAT (SEQ ID NO : 1701)>orf03533MKIMKKKYWTLAILFFCLFNNSVTAQEIPKNLDGNITHTQTSESFSESDEKQVDYSNKNQEEVDQNKFR IQIDKTELFVTTDKHLEKNCCKLELEPQINNDIVNSESNNLLGEDNLDNKIKENVSHLDNRGGNIEHDKDNLESSIV RKYEWDIDKVTGGGESYKLYSKSNSKVSIAILDSGVDLQNTGLLKNLSNHSKNYVPNKGYLGKEEGEEGIISDIQDR LGHGTAVVAQIVGDDNINGVNPHVNINVYRIFGKSSASPDWIVKAIFDAVDDGNDIINLSTGQYLMIDGEYEDGTND FETFLKYKKAIDYANQKGVIIVAALGNDSLNVSNQSDLLKLISSRKKVRKPGLVVDVPSYFSSTISVGGIDRLGNLS DFSNK⑶SDAIYAPAGSTLSLSELGLNNFINAEKYKEDWIFSATLGGYTYLYGNSFAAPKVSGAIAMIIDKYKLKDQ PYNYMFVKKILEETLPVKNGIKVLNIPNVLRYDL匪LQLEYKNEQSWDSFIDNVNLIELEERIQTTIGIKQINTHNI ITIAREGYSQNYLPNTSENTYNSLQVSLVGVLLLFISMVNILffAKKSK (SEQ ID NO: 1702)>orf03543VLKWCILRINHHISRKVDNFLEGTRAHIKGQAHTAWNPLEVPDVRYRSFQFDMSHTLTTNFRTRYFNPT AVTNNSSVTNAFVLTTSTFPVFCRTKDHFIKESFTFWFQGTIIDCFRFFDFSIRP (SEQ ID NO : 1703)>orf03553MPWKELCHKLAPKVFKVIRIYSRENKKSPSNWAFCSFET (SEQ ID NO : 1704)>orf03559VSVLFFCSYFSLSLEKGWFSSLISCKFMNQFLPFCWRQDSPWILTLAQDSITYH(SEQ ID NO: 1705)>orf03564VTDENTRKVRLLVAFFSIVIGYILSSFFISLYHLWQEALRGLL(SEQ ID NO : 1706)>orf03566LHVELIDSHKFNIGRTTCSLLSTTNICKRCQPSINHMS (SEQ ID NO : 1707)>orf03567MLNTNRNELIGTSFLIFCVIYFKDLANIFRTTWNLYIIRQGHYKCQESHNQGRNDV(SEQ ID NO: 1708)>orf03570VNKPILSDIDCHLTNSINLFLPDTQTGNLFWKFNGLIRLAHNHNIFRKKLSLSHFFNICYDLFLGIGRV (SEQ ID NO 1709)>orf03571LKFSNFLGHLDIFSHDGLSLTVSLHQNSTGHATRYCFDR (SEQ ID NO : 1710)[3853]>orf03584VDSLFLSLGEESNQEINLQESFSSTDCNPTLISPETTVAQGLCQDIIYRPFT(SEQ ID NO 1711)>orf03586VNPKSLGSFFLQDSKGFKELVLGHAKLSLPRIVHNVCPQFKNASRIITTRDDFWNACYSLQMFNIFKGI QVNGRTQFTCIGVFLVWRVVGREHNLRTQKVQFMAHQKLYITRAVHTTTFFLENFQNSWSffSSLNCKIFLKALVPRK SLVDGSCLLTNPLLIIQVKGSRELGNNRF(SEQ ID NO 1712)>orf03590MDNLCLHNTffTDffTSIFKQAVVTEDDMTKQNDFFLGIIDAEFHNCLGNFAINESDMSKKITSHCVLCL VWPRQLDDLSQVMQHNPRIEQALIELRINFANSVCQTHHGRRMIGQARFKGMVVGLGSWIGVEFLIILGVEISDNP LPDRIFNFENHLRHVVTNFLDINW(SEQ ID NO :768)>orf03591LIDLRGIVINFSASFHVDNLTCGKGLNVMRLGIPELPINLATIILEGKG(SEQID NO 1713)>orf03604MDALVLQKNQETIQQIAVKIRFLDGHDYYSLIDIDNRRTNQTVFPFVNFEDIAF(SEQ ID NO: 1714)>orf03605MAFFTEIPTRACLINLAITLHIVETCQGFNDLSLHLRVLAL (SEQ ID NO 1715)>orf03609MLLPLPFNTSKIKQIAMHSDLNQKEMIGHIFHDEDIF (SEQ ID NO : 1716)>orf03614MKQTVKKLALVASIAATLGGGVSVASAAVQYPEGGVWTYGSGNGGAYSNYYHPSKYHSSTVVSRKTGSS DKGYAGAGGTSRAffIRTSffGEKVAFYYNV (SEQ ID NO: 1717)>orf03643LVEQLTFNQWVTGSSPVRVIYAGLAELADAPDLGSGA (SEQ ID NO : 1718)>orf03675MKELLNKAFFNKNKASLSKEVLLELQGKRLPVNLFLSKSLFQASL(SEQ ID NO : 1719)>orf03690MMTKIKLTIDIIMPCRHITNIWIYKEEGRVNLFFYSQIFFDAIDERIIHNFNSKYHLSFFSPVTGFSQI FDKTLACLG (SEQ ID NO : 1720)>orf03695LHTSFRSSVGHSHTffHQDIVRPILFSRFNDSIVILffQNCPTFN (SEQ ID NO 1721)>orf03713MLEQARLKVEQQAIKNIQFLEQDLPKNPLEKEFDCLAVSRVLHHMPDLDAALSLFHQHLKEDGKLIIAD FTRTEANHHGFDLAELENKLIEHGFSSVHSQILYSAEDLFQGNHSEFFLIVAQKSLA(SEQ ID NO 1722)>orf03714MKHDFNHKAETFDSPKNIFLANLVCQAAEKQIDLLSDKEILDFGGGTGLLALPLTPSQAG (SEQ ID NO 1723)>orf03716VWKKKKVKAGVLLYAVTIAAIFSLLLQFYLNRQIAHYQDYALNKEKLVAFAMAKRTKDKAEQESGEQVFNLGQVSYQNKKTSLVTTVRTSKSQYEFLFPSVKIKEEKRDKKEEVATDSSEKAEKKNQKRSLKRKRIPSQFNYNA LNPE (SEQ ID NO 1724)>orf03718MVDLQSFFTRKYLNLNSVDAYLILPRLQGHLSYPQDFFLLQDFCFLLPIFLNLSQKEGRNAGKDS (SEQ ID NO 1725)>orf03733MRIRNSPFDHILQTIFEFEDRTCQVTCRFEACSSICNDNWEFSQHIISVFQSPSCHTVCDKSDVFCSF LFDKNFASLWIYVVTITDQLCIGMWQLVHGSNHTQFTVSQPTHSIVGMHPNTRSSIDCFFGFIKSRV (SEQ ID NO 1726)>orf03734MSKSNRHTFARNCTNKVFHPITFffCKGNFIKQAICRFLPRMKLLNTRVSHISffILCPLKSFCEIffTFII NPTNLSTCCFFIMVSKIFSDCKQLLISGC (SEQ ID NO: 1727)>orf03736MQCTFNVWHHIYTCISM 匪 SIHKTWGNAITCIVNHLSPFRNLLYMFPKLAVHKFQVTTSTNSVWVEKL IRFNIVRHNVNLLKRLILQFIMSITL (SEQ ID NO: 1728)>orf03750MKKRMLLASTVALSFAPVLATQAEEVLWTARSVEQIQNDLTKTDNKTSYTVQYGDTLSTIAEALGVDVT VLANLNKITNMDLIFPETVLTTTVNEAEEVTEVEIQTPQADSSEEVTTATADLTTNQVTVDDQTVQVADLSQPIAEV TKTVIASEEVAPSTGTSVPEEQTTETTRPVEEATPQETTPAEKQETQASPQAASAVEVTTTSSEAKEVASSNGATAA VSTYQPEETKIISTTYEAPAAPDYAGLAVAKSENAGLQPQTAAFKEEIANLFGITSFSGYRP⑶SGDHGKGLAIDFM VPERSEL⑶KIAEYAIQNMASRGISYIIWKQRFYAPFDSKYGPANTWNPMPDRGSVTENHYDHVHVSMNG (SEQ ID NO 1729)>orf03763VLAEADALVDAEAEALVDAEADALVLAEAEALVDADS DALVDAEADALVDAEAEALVDADSDADVLAD TEAEALVDAEADALVLVDADVLALVDADVLADVLALVDADVLAEAEALVLAEAEALVDAEAEALVDADS DAEVLAE ADALVLAEADALVDAEAEALVDAEAEALVDAXXHS FIN (SEQ ID NO : 1730)>orf03764VRRLQHRQVLQLQRQPVRRLQRQPVRQPQQAPVLRLQQVLAPQPQHQQVLRSQRQPVPLNPHQPVHRLQ QVLAPQLQHQRVLQLSMNQCVGIRINQCIGFSKY (SEQ ID NO: 1731)>orf03766VRRNPHQPVHRLQQVLVHQLQHQRVLRLQQAPVRLNPHQRLPQPQQVPVRQLQQVLVHQLPHQQVLQLQ RQPAPQPQQVPVRQLQQAQAPLSQRQPVRQLQXXXFHSLIN(SEQ ID NO : 1732)>orf03772VTDENTRKVRLLVAFFSIVIGYILSSFFISLYHLWQEALRGLL (SEQ ID NO : 1733)>orf03774MNXXALVDAEAEADVDAEAEALVDADAEALVLAEADALVDADSDADVLAEAEALVDAEADALIDADSE ADVLAEAEALVDAEADALVDAEAEALVLADAEALVDAEADALVDAEADALVDAEADALVDAEAEALVDAEADALVL AEAEALVDAEADALVDADS DAEVLVLAEAEALVDAEADALVDADSDAEILAEADALVDAEAEALVLADSDALVNAE ADVLAEADALVDADSEALVLAEADALVLAEAEALVDAEAEGTGMRKLIH (SEQ ID NO : 1734)[3903]>orf03777VLALVDADVLADVLALVDADVLAEAEALVLAEAEALVDAEAEALVDADS DAEVLAEADALVLAEADAL VDAEAEALVDAEAEALVDAEAEALVDADS DADVLAEADALVDAEADALVLAEADALVLAEADALVDADSEALVDAE AEALVDAEAEALVDAEAEALVDAEAEALVDAEAEADVDAEAEALVDADAEALVLAEADALVDADSNADVLAEAEALV DAEXXIPFIN(SEQ ID NO: 1735)>orf03794MKIKEQTRKLAVGCLKQCFEVVDRTDEVSSKYCFEVADGS (SEQ ID NO 1736)>orf03804 [3908]LLGSFFSffTTKELMGIIFFNNFPTVHKNNMIGYISSKTYLIKLIKNSI(SEQ ID NO : 1737)>orf03818MEKILLHNLNQTEFFINKAIGWTLRDYSKTNPTWVTCFIEKNKERMAELSIKEASKYL(SEQ ID NO: 1738)>orf03819MSLADLLEELEAAKDSKKARSMEAYMRHQFSFLGIAVPERNKLYKNIFQKRKKQRLSIGILQTLAGKRI LENTNMWLLTI (SEQ ID NO : 1739)>orf03829MTTGWFQVNGRWYYAYSSGALAVNTTVDGYSVNYNGEWAQ (SEQ ID NO : 1740)>orf03851MAFTTEELLNLGLTEEQAKSVFALRGKELNEDKSALETIKQERDSLKSQLQKAEEQVEHLKSLENISA EQKDAIDKLQAEYDKYKNEAAAELAQTKKVSAISLALKDTNAFNPDKLMKFIDVDAIQIDDNGKPQIDEVINGIKE SDPHLFQAEESKPSPNIFPLR(SEQ ID NO : 1741)>orf03853MGSSGEMRTRPAEELGVDTFYYSMKAMARPACSPLQGQIVTKGTGREIDGITIYSLLDYGYGTAAGCLG IHCGHYLTPFIVGVHELPNLPDYLKNLTPEQAEENARIEAGQRGLERLIKTHKERLHYAHTLQDDKMIQAERLKVRG YQTKIRNLINQHDFLTRDYRREKLYIS(SEQ ID NO: 1742)在一些實(shí)施方式中,優(yōu)選的23F抗原選自以下多肽或其免疫原性片段 orf01158(SEQ ID NO 1297)、orf01305 (SEQ ID NO 1309)、orf01307 (SEQ ID NO: 1311)、 orf01631(SEQ ID NO : 1343)、orf01804 (SEQ ID NO : 1362)、orf01807 (SEQID NO: 1364)、 orf02164(SEQ ID NO : 1434)、orf02189 (SEQ ID NO : 1451)、orf02194 (SEQ ID NO: 1455)、 orf02219(SEQ ID NO : 1466)、orf02221 (SEQ ID NO : 1467)、orf02224 (SEQ ID NO: 1470)、 orf02228(SEQ ID NO : 1474)、orf02242 (SEQ ID NO : 1484)、orf02244 (SEQ ID NO: 1485)、 orf02246(SEQ ID NO 1486),orf02247(SEQID NO1487),orf02652(SEQ ID NO: 1491)。實(shí)施例3 菌毛粘附菌毛2介導(dǎo)對(duì)肺泡上皮細(xì)胞A459的粘附。雙標(biāo)記染色顯示,菌毛2_陽(yáng)性菌株粘 附于A549細(xì)胞表面,菌毛(用標(biāo)記的抗-01287抗體觀察)接觸細(xì)胞。并且,菌毛的等基因敲除突變體在宿主細(xì)胞相互作用方面顯著受損。圖2顯示,與 菌毛陽(yáng)性菌株(PNllO)相反,菌毛陰性菌株(D39)沒(méi)能結(jié)合A549細(xì)胞。PWlO中敲除菌毛 消除了其結(jié)合能力。在蓋玻片上用01287純化蛋白培養(yǎng)A459細(xì)胞,通過(guò)共聚焦顯微鏡觀察顯示結(jié)合水平低。該觀察結(jié)果通過(guò)以下試驗(yàn)得到證實(shí)將蛋白質(zhì)與懸浮培養(yǎng)細(xì)胞一起培育,通過(guò)FACS 分析對(duì)粘附水平進(jìn)行定量(圖4)。使用肺炎球菌菌毛I(xiàn)RrgA亞單位作為陽(yáng)性對(duì)照,綠色熒 光蛋白(GFP)用作陰性對(duì)照。通過(guò)共聚焦顯微鏡對(duì)純化的菌毛進(jìn)行成像。顯示粘附于在蓋玻片上生長(zhǎng)的A549 細(xì)胞。并且,當(dāng)加入表達(dá)菌毛I(xiàn)I的菌株時(shí),純化菌毛對(duì)呼吸道細(xì)胞的粘附似乎有所增加。 這種作用可能是因?yàn)榧兓c細(xì)菌和A549細(xì)胞間的相互作用。純化菌毛不能增加菌毛 2的等基因敲除突變體對(duì)呼吸道細(xì)胞的粘附(圖3)。實(shí)施例4 :INV104B的其他序列下面提供了 L印A肽酶(orf01289)的示例性核酸序列 ATGCTGCTTAAAAAGAAACATAAGAAACCAGTAACACAAGTCAATCGGGATAAGTCTCCGCCGAGTGTC TGGGGAGATATCCTTTACTTAGTCAGTAAACTTCTGATGGTTGGATTTGTACTAGCCATCCTTTACTTTTTCGTCTT TGGATTATTAAGATACAATGACGATGGCATGAAGCCCGCCTTAAAAGATGGCGACTTGGTCGTCTATTATAGGTTGG ATAAACGCTATTCGATTGGTGATTTGCTAGTCTATAGTTATAAAGGTAAGGAAAGAGTGGCGCGTGTCATAGCAACC GAAGGAAGTACAATCGATATAAACGAAAATGGTCTCATCATCAACGGTTCTCCTCAACAAGAGCAAGATATCTACAA AGAAACGCTGCTCTATAAGGAAGGGGCAACCTTCCCGATGAAAGTCCCAGCAGGACAACTTTTTGTCCTCGGGGACA ATCGAACAACGGCTGTAGACAGTCGTGCTTTTGGAACCATCCCTATACAGGATACTCAAGGCAAAGTTGTAACAGTC ATTAGAAGACGAGGCTTT (SEQ ID NO: 1743)下面提供了 L印A肽酶的示例性氨基酸序列MLLKKKHKKPVTQVNRDKSPPSVWGDILYLVSKLLMVGFVLAILYFFVFGLLRYNDDGMKPALKDGDLV VYYRLDKRYSI⑶LLVYSYKGKERVARVIATEGSTIDINENGLIINGSPQQEQDIYKETLLYKEGATFPMKVPAGQL FVL⑶NRTTAVDSRAFGTIPIQDTQGKWTVIRRRGF (SEQ ID NO 673)下面提供了分選_l(orf01285)的示例性核酸序列ATGATGAAAACCAAGCGTGAGAAACCAAAAAAGAGTCTGTCTAGGCGTCTCGTTCTTGCTGTGGATGGG GTGATCAATCACTTGCTGCTCATTTTTGCAGCTTTGATCTTTCTCTTTGGTTTCTACGCCCTTTGGGATTCCAACCA AGTCTACTCCTTAGCTTCGTCAAGTGAGTACGAAGCTTATCGACCTGTCACGACGCAACAGGATGAGCTGGCCAGTT TTTCAGGCTTCAGCAAACTCCAAGAACTCAATCCCGAAGTCCTCGGTTGGATCAATGTCTATGGCACCAATATCGAC TATCCCTTAGTCCAAGCCAAGGACAATGAAAAGTATCTCAACAAGGACTCCAAAGGTGAGTTTGCAGCGACAGGCGC TATCTTTCTCGATGCACGAAATAATCCTAAGTTCGAAGACTTTAATACCATTATCTACGGGCACCACGTAGAAAATG GGGTCATGTTTGGTGATGTGGCTAAGTTTGCTGATCAGGAATTTTTTGACCAGCATCGTTACGGTAGTATATACTAC AATGGTGTGGAAAAAGGGCTCGAGATCTTTGAGATGTTGGAGGTTGATGCCTATGACTTTAACATCTATGATCCAGG AATACAGGGTGAGGACCGCCAGCAGGCCTATCTAGACCACCTGCTCTCAGTCGCCATGCACAAGCGGGATATCTCAC TCTCACCGAGTGATCGTATCATCCTACTCAGTACCTGTTTTCTCGATGTGACCAATGGTCGTCATATCGTAGTCGCA AAGATTACAGACACCGTCCCTAAAAATACTTTCCATACAAAAAAATCAAAACCATTTCCATACAGTGTCTTTGATGA CTCGTCTCTTGGACGTTTCCTCTCATCAATCCCACTATGGATTTGGTACCTTATCTTGTTTGTATTGTTCTTGCTCT TGATTTTCTTACTCCTTGTCCTCTACTTGATCCTACGTCGTAGAAGAGAGAGTAAAAAAAAATGCAAGAAGCAGACC CTTTTACTGACTAAGGGTGAATAGAAA (SEQ IDNO 1744)下面提供了分選-1的示例性氨基酸序列MMKTKREKPKKSLSRRLVLAVDGVINHLLLIFAALIFLFGFYALWDSNQVYSLASSSEYEAYRPVTTQQ DELASFSGFSKLQELNPEVLGWINVYGTNIDYPLVQAKDNEKYLNKDSKGEFAATGAIFLDARNNPKFEDFNTIIYGHHVENGVMFGDVAKFADQEFFDQHRYGSIYYNGVEKGLEIFEMLEVDAYDFNIYDPGIQGEDRQQAYLDHLLSVAMH KRDISLSPSDRIILLSTCFLDVTNGRHIVVAKITDTVPKNTFHTKKSKPFPYSVFDDSSLGRFLSSIPLWIWYLILF VLFLLLIFLLLVLYLILRRRRESKKNARSRPFY (SEQ IDNO 676)下面提供了分選-2 (orf01282)的示例性核酸序列ATGACGGTTCAAAAAAGAGCGCGATTTAAAAACGTATTTCTGGTATTCTTCTGTGTTTTTGTAGCTCTT TTTAGTTGGCAGAGAGTAGTAGAAGCAAGTGACTATGATCACTATAATCCTATTGAAAAGGATGCTTCGAGCACAGG TTTTGAAACCCTACAGCACTTGAACAAAGATGTTTGCGGTTGGATTAGCCTTGATGGGACCAAGGTAGACTATCCGC TTCTACAAAGTCAGGATAATGTCAAATACCTTGACCGCAATGCCTTTGGCGATTATACGATAATGGGATCAATTTTT CTCGACTATCGCTTTAATCCCAACTTTACTGATTTTAATACGATCATCTACGGACACTCTATGGCTTCAGGGGCTAT GTTCGGTGAGATTAAGAAATTTGCTGATAAGGAATTCTTCGACCAGCATCGCTACGGTTCTATCTACTACAATGGT CGAGAACGTGGTCTTGAAATTTTTGGGATTTTAGAAGTGGATGCCTATGACACGGAGATTTATCGAACCTTGAGTT CCAAGGATGAGGAACACCAGGCTTACTATCAATATCTGCTAAGTAAAGCCAAGTACAAGCGAGATGTTTCCTTAACA (SEQ ID NO: 1745) [3936]下面提供了分選_2的示例性氨基酸序列MTVQKRARFKNVFLVFFCVFVALFSWQRVVEASDYDHYNPIEKDASSTGFETLQHLNKDVCGWISLDGT KVDYPLLQSQDNVKYLDRNAF⑶YTIMGSIFLDYRFNPNFTDFNTIIYGHSMASGAMFGEIKKFADKEFFDQHRYGS IYYNGRERGLEIFGILEVDAYDTEIYRTLSSKDEEHQAYYQYLLSKAKYKRDVSLT (SEQ ID NO 1123)描述了許多本發(fā)明方法和組合物的實(shí)施方式。然而,應(yīng)理解,可進(jìn)行各種改進(jìn)而不 背離本發(fā)明的精神和范圍。
權(quán)利要求
一種由肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的分離菌毛。
2.如權(quán)利要求1所述的菌毛,其特征在于,所述菌毛包含分選酶。
3.如權(quán)利要求1所述的菌毛,其特征在于,所述菌毛包含LPXTG細(xì)胞壁錨定蛋白。
4.如權(quán)利要求1所述的菌毛,其特征在于,所述菌毛通過(guò)酶消化或機(jī)械剪切從細(xì)胞分罔。
5.如權(quán)利要求1所述的菌毛,其特征在于,所述機(jī)械剪切包括超聲處理。
6.如權(quán)利要求1所述的菌毛,其特征在于,所述菌毛基本上不含細(xì)菌細(xì)胞。
7.一種免疫原性組合物,其包含一種或多種如權(quán)利要求1所述的菌毛。
8.一種制備如權(quán)利要求1所述菌毛的方法,所述方法包括使產(chǎn)生菌毛的細(xì)菌細(xì)胞經(jīng)受 酶消化或機(jī)械剪切和從所述細(xì)胞分離所述菌毛。
9.一種分離的肺炎鏈球菌分選酶,其特征在于,所述分選酶是SEQ IDNO :282、SEQ ID NO 1386, SEQ ID NO 676 或 SEQ ID N0:1123 之一。
10.一種分離的肺炎鏈球菌LPXTG細(xì)胞壁錨定蛋白,其特征在于,所述LPXTG細(xì)胞壁錨 定蛋白是 SEQ ID N0:2、SEQ ID N0:4、SEQ ID N0:6、SEQ IDNO :7、SEQ ID NO :8 或 SEQ ID NO :9 之一。
11.一種分離肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛的方法,所述方法包括使產(chǎn)生肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛的細(xì)菌細(xì)胞經(jīng)受酶消化或機(jī)械剪切;禾口從所述細(xì)胞分離所述菌毛。
12.如權(quán)利要求11所述的方法,其特征在于,所述機(jī)械剪切包括超聲處理。
13.如權(quán)利要求11所述的方法,其特征在于,所述酶消化采用變?nèi)芫剡M(jìn)行。
14.如權(quán)利要求11所述的方法,其特征在于,所述分離包括一次或多次密度梯度離心。
15.如權(quán)利要求11所述的方法,其特征在于,所述分離包括降低多分散性。
16.如權(quán)利要求15所述的方法,其特征在于,根據(jù)大小分離組分來(lái)降低多分散性。
17.一種抗體,所述抗體特異性結(jié)合肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛。
18.如權(quán)利要求17所述的抗體,其特征在于,所述抗體是單克隆抗體、多克隆抗體、嵌 合抗體、人抗體、人源化抗體、單鏈抗體或Fab片段。
19.如權(quán)利要求17所述的抗體,其特征在于,所述抗體是標(biāo)記的。
20.如權(quán)利要求19所述的抗體,其特征在于,所述標(biāo)記是酶、放射性同位素、造影劑、毒 素或熒光團(tuán)。
21.如權(quán)利要求17所述的抗體,其特征在于,所述抗體特異性結(jié)合一種或多種由肺炎 鏈球菌菌毛I(xiàn)I島(INV104B)編碼的LPXTG細(xì)胞壁錨定蛋白。
22.如權(quán)利要求17所述的抗體,其特征在于,所述抗體特異性結(jié)合一種或多種選自下 組的 LPXTG 細(xì)胞壁錨定蛋白SEQ ID NO :2、SEQ ID NO :4、SEQID NO :6、SEQ ID NO :7、SEQ ID NO 8 或 SEQ ID NO :9。
23.如權(quán)利要求17所述的抗體,其特征在于,所述抗體特異性結(jié)合一種或多種選自下 組的分選酶SEQ ID NO 282, SEQ ID N0:1386、SEQ ID NO 676 或 SEQ ID NO :1123。
24.—種免疫原性組合物,其包含寡聚形式的純化的肺炎鏈球菌菌毛I(xiàn)I島(INV104B) 多肽。
25.如權(quán)利要求24所述的免疫原性組合物,其特征在于,所述寡聚形式是高寡聚體。
26.如權(quán)利要求24所述的免疫原性組合物,其特征在于,所述多肽是由肺炎鏈球菌菌 毛I(xiàn)I島(INV104B)編碼的LPXTG細(xì)胞壁錨定蛋白的片段。
27.如權(quán)利要求26所述的免疫原性組合物,其特征在于,所述片段的長(zhǎng)度是至少100個(gè)毗連氨基酸殘基。
28.如權(quán)利要求26所述的免疫原性組合物,其特征在于,所述片段的長(zhǎng)度是至少50個(gè)毗連氨基酸殘基。
29.如權(quán)利要求26所述的免疫原性組合物,其特征在于,所述片段的長(zhǎng)度是至少20個(gè)毗連氨基酸殘基。
30.如權(quán)利要求26所述的免疫原性組合物,其特征在于,所述片段保留共價(jià)結(jié)合肽聚 糖細(xì)胞壁的能力。
31.如權(quán)利要求26所述的免疫原性組合物,其特征在于,所述片段保留通過(guò)LPXTG基序 與另一片段或蛋白質(zhì)交聯(lián)的能力。
32.如權(quán)利要求24所述的免疫原性組合物,其特征在于,所述多肽包含兩個(gè)或多個(gè)肺 炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的LPXTG細(xì)胞壁錨定蛋白的片段。
33.一種誘導(dǎo)針對(duì)肺炎鏈球菌的免疫應(yīng)答的方法,所述方法包括給予對(duì)象有效量的肺 炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛。
34.如權(quán)利要求33所述的方法,其特征在于,所述菌毛是分離的。
35.如權(quán)利要求33所述的方法,其特征在于,所述對(duì)象是人。
36.一種檢測(cè)對(duì)象肺炎鏈球菌感染的方法,所述方法包括分析來(lái)自所述對(duì)象的樣品中 是否存在針對(duì)肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛的抗體。
37.如權(quán)利要求36所述的方法,其特征在于,與菌毛組分相比,所述抗體優(yōu)先結(jié)合菌毛 復(fù)合物。
38.如權(quán)利要求36所述的方法,其特征在于,所述樣品是血清。
39.如權(quán)利要求36所述的方法,其特征在于,所述對(duì)象是人。
40.一種檢測(cè)對(duì)象肺炎鏈球菌感染的方法,所述方法包括使樣品與權(quán)利要求17所述的 抗體相接觸并檢測(cè)抗體與樣品組分的結(jié)合。
41.如權(quán)利要求40所述的方法,其特征在于,與菌毛組分相比,所述抗體優(yōu)先結(jié)合菌毛 復(fù)合物。
42.如權(quán)利要求40所述的方法,其特征在于,所述樣品是血清。
43.如權(quán)利要求40所述的方法,其特征在于,所述對(duì)象是人。
44.一種治療患有肺炎鏈球菌感染的對(duì)象的方法,所述方法包括給予所述對(duì)象有效量 的能夠特異性結(jié)合肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛的試劑。
45.如權(quán)利要求44所述的方法,其特征在于,所述試劑是抗體。
46.如權(quán)利要求45所述的方法,其特征在于,所述抗體是單克隆抗體、多克隆抗體、嵌 合抗體、人抗體、人源化抗體、單鏈抗體或Fab片段。
47.如權(quán)利要求45所述的方法,其特征在于,所述抗體阻斷肺炎鏈球菌與細(xì)胞的結(jié)合。
48.如權(quán)利要求47所述的方法,其特征在于,所述細(xì)胞是上皮細(xì)胞。
49.如權(quán)利要求48所述的方法,其特征在于,所述上皮細(xì)胞是肺或鼻咽上皮細(xì)胞。
50.如權(quán)利要求45所述的方法,其特征在于,所述抗體特異性結(jié)合一種或多種由肺炎 鏈球菌菌毛I(xiàn)I島(INV104B)編碼的LPXTG細(xì)胞壁錨定蛋白。
51.如權(quán)利要求47所述的方法,其特征在于,在測(cè)定肺炎鏈球菌與A549肺上皮細(xì)胞結(jié) 合的試驗(yàn)中測(cè)得,與對(duì)照相比,所述抗體阻斷至少50%肺炎鏈球菌與所述細(xì)胞的結(jié)合。
52.如權(quán)利要求44所述的方法,其特征在于,所述對(duì)象是人。
53.一種確定肺炎鏈球菌感染患者的療程的方法,所述方法包括分析來(lái)自所述對(duì)象的樣品中是否存在針對(duì)肺炎鏈球菌菌毛Π島(INV104B)編碼菌毛 的抗體;和如果檢測(cè)到存在所述抗體則給予所述對(duì)象抗炎藥。
54.如權(quán)利要求53所述的方法,其特征在于,所述對(duì)象是人。
55.一種檢測(cè)肺炎鏈球菌感染患者的療程的方法,所述方法包括分析來(lái)自所述對(duì)象的樣品中是否存在針對(duì)肺炎鏈球菌菌毛Π島(INV104B)編碼菌毛 的抗體;和如果沒(méi)有檢測(cè)到所述抗體的存在則給予所述對(duì)象抗生素。
56.如權(quán)利要求55所述的方法,其特征在于,所述對(duì)象是人。
57.一種分離的菌毛或菌毛樣多聚體,其包含多肽,所述多肽包含具有最多30個(gè)氨基 酸取代、插入或缺失的肺炎鏈球菌菌毛Π島(INV104B)編碼菌毛蛋白的氨基酸序列。
58.如權(quán)利要求57所述的菌毛或菌毛樣多聚體,其特征在于,最多具有20個(gè)氨基酸取 代、插入或缺失。
59.如權(quán)利要求57所述的菌毛或菌毛樣多聚體,其特征在于,最多具有10個(gè)氨基酸取 代、插入或缺失。
60.如權(quán)利要求57所述的菌毛或菌毛樣多聚體,其特征在于,最多具有5個(gè)氨基酸取 代、插入或缺失。
61.如權(quán)利要求57-60中任一項(xiàng)所述的多肽,其特征在于,所述氨基酸取代、插入或缺 失是氨基酸取代。
62.如權(quán)利要求61所述的多肽,其特征在于,所述氨基酸取代是保守性氨基酸取代。
63.如權(quán)利要求57所述的多肽,其特征在于,所述蛋白質(zhì)是LPXTG細(xì)胞壁錨定蛋白。
64.一種多肽,其包含肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的一種或多種LPXTG細(xì)胞 壁錨定蛋白的氨基酸序列或其免疫原性片段。
65.如權(quán)利要求64所述的多肽,其特征在于,所述多肽包含兩種或多種LPXTG細(xì)胞壁錨 定蛋白的氨基酸序列或其免疫原性片段。
66.一種純化多肽,其氨基酸序列由SEQ ID NO:2構(gòu)成。
67.一種純化多肽,其包含SEQ ID NO 2的至少10個(gè)連續(xù)殘基。
68.一種純化多肽,其氨基酸序列包含與SEQ ID NO :2至少85%相同的序列。
69.如權(quán)利要求68所述的純化多肽,其特征在于,所述序列與SEQIDNO :2至少90%相同。
70.如權(quán)利要求68所述的純化多肽,其特征在于,所述序列與SEQIDNO :2至少95%相同。
71.—種純化多肽,其氨基酸序列由SEQ ID N0:4構(gòu)成。
72.一種純化多肽,其包含SEQ ID NO 4的至少10個(gè)連續(xù)殘基。
73.一種純化多肽,其氨基酸序列包含與SEQ ID NO 4至少85%相同的序列。
74.如權(quán)利要求73所述的純化多肽,其特征在于,所述序列與SEQIDNO 4至少90%相同。
75.如權(quán)利要求73所述的純化多肽,其特征在于,所述序列與SEQIDNO :4至少95%相同。
76.一種純化多肽,其氨基酸序列由SEQ ID N0:6構(gòu)成。
77.一種純化多肽,其包含SEQ ID NO 6的至少10個(gè)連續(xù)殘基。
78.一種純化多肽,其氨基酸序列包含與SEQ ID NO :6至少85%相同的序列。
79.如權(quán)利要求78所述的純化多肽,其特征在于,所述序列與SEQIDNO :6至少90%相同。
80.如權(quán)利要求78所述的純化多肽,其特征在于,所述序列與SEQIDNO :6至少95%相同。
81.—種純化多肽,其氨基酸序列由SEQ ID N0:7構(gòu)成。
82.一種純化多肽,其包含SEQ ID NO 7的至少10個(gè)連續(xù)殘基。
83.一種純化多肽,其氨基酸序列包含與SEQ ID NO :7至少85%相同的序列。
84.如權(quán)利要求83所述的純化多肽,其特征在于,所述序列與SEQIDNO 7至少90%相同。
85.如權(quán)利要求83所述的純化多肽,其特征在于,所述序列與SEQIDNO :7至少95%相同。
86.一種純化多肽,其氨基酸序列由SEQ ID N0:8構(gòu)成。
87.一種純化多肽,其包含SEQ ID NO 8的至少10個(gè)連續(xù)殘基。
88.一種純化多肽,其氨基酸序列包含與SEQ ID NO :8至少85%相同的序列。
89.如權(quán)利要求88所述的純化多肽,其特征在于,所述序列與SEQIDNO :8至少90%相同。
90.如權(quán)利要求88所述的純化多肽,其特征在于,所述序列與SEQIDNO :8至少95%相同。
91.一種純化多肽,其氨基酸序列由SEQ ID N0:9構(gòu)成。
92.一種純化多肽,其包含SEQ ID NO 9的至少10個(gè)連續(xù)殘基。
93.一種純化多肽,其氨基酸序列包含與SEQ ID NO :9至少85%相同的序列。
94.如權(quán)利要求93所述的純化多肽,其特征在于,所述序列與SEQIDNO 9至少90%相同。
95.如權(quán)利要求93所述的純化多肽,其特征在于,所述序列與SEQIDNO :9至少95%相同。
96.一種純化多肽,其氨基酸序列包含與選自SEQ ID N0:29到SEQ IDNO :1742或其免 疫原性片段的序列至少85%相同。
97.如權(quán)利要求96所述的純化多肽,其特征在于,所述序列至少90%相同。
98.如權(quán)利要求96所述的純化多肽,其特征在于,所述序列至少95%相同。
99.如權(quán)利要求96所述的純化多肽,其特征在于,所述序列選自SEQIDNO 29到SEQID NO :1742。
100.一種純化多肽,其氨基酸序列與選自下組的序列至少85%相同SEQID NO :53、 SEQ ID N0:65、SEQ ID NO 70、SEQ ID NO 99、SEQ ID NO 104,SEQ ID NO 117、SEQ ID NO: 135,SEQ ID NO 177,SEQ ID NO 178,SEQ IDNO 198,SEQ ID NO 235,SEQ ID NO 236,SEQ ID NO 237,SEQ ID NO 242、SEQ ID NO 247、SEQ ID NO 248、SEQ ID NO 250、SEQ ID NO: 25USEQ IDNO 252,SEQ ID NO 253、SEQ ID NO :433、SEQ ID NO 439、SEQ ID NO 444、SEQ ID NO 538,SEQ ID NO 539,SEQ ID NO 540,SEQ ID N0:541、SEQ IDNO 542,SEQ ID NO: 543、SEQ ID NO 544, SEQ ID NO 545, SEQ ID NO 581 禾口 SEQ ID NO :593,或它們的免疫原 性片段。
101.如權(quán)利要求100所述的純化多肽,其特征在于,所述序列至少90%相同。
102.如權(quán)利要求100所述的純化多肽,其特征在于,所述序列至少95%相同。
103.—種純化多肽,其氨基酸序列與選自下組的序列至少85%相同SEQID NO :626、 SEQ ID NO 628,SEQ ID NO 629,SEQ ID NO 630,SEQ ID NO :63USEQ ID NO :632、SEQ ID NO :639、SEQ ID NO :645、SEQ ID NO :747、SEQ ID NO :751、SEQ ID NO :752、SEQ ID NO 783,SEQ ID NO 786,SEQID NO 787,SEQ ID NO :810、SEQ ID NO :812、SEQ ID NO :813、SEQ ID NO 824,SEQ ID NO :831、SEQ ID NO : 842、SEQ ID NO :847、SEQ ID NO :875、SEQ ID NO: 876,SEQ ID NO 879,SEQ ID NO :880,SEQ ID NO 882,SEQ IDNO :913、SEQ ID NO :914,SEQ ID NO :925,SEQ ID NO :926、SEQ ID NO 947,SEQ ID NO :948、SEQ ID NO : 968、SEQ ID NO: 987、SEQ ID NO 988,SEQ IDNO990,SEQ ID NO 992,SEQ ID NO 1003,SEQ ID N0:1007、 SEQ ID NO 1008,SEQ ID NO 1036,SEQ ID NO 1082,SEQ ID N0:1120和SEQ ID NO :1123, 或它們的免疫原性片段。
104.如權(quán)利要求103所述的純化多肽,其特征在于,所述序列至少90%相同。
105.如權(quán)利要求103所述的純化多肽,其特征在于,所述序列至少95%相同。
106.—種純化多肽,其氨基酸序列與選自下組的序列至少85%相同SEQID NO 1297、 SEQ ID NO :1309、SEQ ID NO :1311、SEQ ID NO :1343、SEQ IDNO :1362、SEQ ID NO :1364、 SEQ ID NO 1434,SEQ ID NO 1451、SEQ ID NO 1455、SEQ ID NO 1466,SEQ ID NO 14678, SEQ ID N0:1470、SEQ ID N0:1474、SEQ ID N0:1484、SEQ ID N0:1485、SEQ ID N0:1486、 SEQ ID N0:1487和SEQ ID NO :1491,或它們的免疫原性片段。
107.如權(quán)利要求106所述的純化多肽,其特征在于,所述序列至少90%相同。
108.如權(quán)利要求106所述的純化多肽,其特征在于,所述序列至少95%相同。
109.一種編碼權(quán)利要求64所述多肽或其免疫原性片段的多核苷酸。
110.一種純化抗體,所述抗體通過(guò)用如權(quán)利要求64所述的多肽免疫對(duì)象而獲得。
111.一種誘導(dǎo)針對(duì)肺炎鏈球菌的免疫應(yīng)答的方法,所述方法包括給予對(duì)象有效量的如 權(quán)利要求64所述的多肽。
112.—種肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的LPXTG細(xì)胞壁錨定蛋白的免疫原性 片段。
113.—種分離多核苷酸,所述多核苷酸編碼如權(quán)利要求57-65或112中任一項(xiàng)所述的 多肽或片段。
114.一種分離核酸,其多核苷酸序列由SEQ ID NO :1或SEQ ID NO :1的簡(jiǎn)并變體構(gòu)成。
115.一種分離核酸,其包含在嚴(yán)謹(jǐn)條件下與雜交探針雜交的序列,所述探針的核苷酸 序列由SEQ ID NO :1或SEQ ID NO 1的互補(bǔ)序列構(gòu)成。
116.一種分離核酸,其包含編碼氨基酸序列與SEQ ID NO :2至少85%相同的多肽的序列。
117.如權(quán)利要求116所述的分離核酸,其特征在于,所述氨基酸序列與SEQID N0:2至 少90%相同。
118.如權(quán)利要求116所述的分離核酸,其特征在于,所述氨基酸序列與SEQID N0:2至 少95%相同。
119.一種分離核酸,其多核苷酸序列由SEQ ID NO :3或SEQ ID NO :3的簡(jiǎn)并變體構(gòu)成。
120.一種分離核酸,其包含在嚴(yán)謹(jǐn)條件下與雜交探針雜交的序列,所述探針的核苷酸 序列由SEQ ID NO 3或SEQ ID NO 3的互補(bǔ)序列構(gòu)成。
121.—種分離核酸,其包含編碼氨基酸序列與SEQ ID NO :4至少85%相同的多肽的序列。
122.如權(quán)利要求121所述的分離核酸,其特征在于,所述氨基酸序列與SEQID NO :4至 少90%相同。
123.如權(quán)利要求121所述的分離核酸,其特征在于,所述氨基酸序列與SEQID NO :4至 少95%相同。
124.—種分離核酸,其多核苷酸序列由SEQ ID NO :5或SEQ ID NO :5的簡(jiǎn)并變體構(gòu)成。
125.—種分離核酸,其包含在嚴(yán)謹(jǐn)條件下與雜交探針雜交的序列,所述探針的核苷酸 序列由SEQ ID NO 5或SEQ ID NO 5的互補(bǔ)序列構(gòu)成。
126.—種分離核酸,其包含編碼氨基酸序列與SEQ ID NO :6至少85%相同的多肽的序列。
127.如權(quán)利要求121所述的分離核酸,其特征在于,所述氨基酸序列與SEQID N0:6至 少90%相同。
128.如權(quán)利要求121所述的分離核酸,其特征在于,所述氨基酸序列與SEQID N0:6至 少95%相同。
129.—種分離核酸,其包含編碼氨基酸序列與SEQ ID NO :7至少85%相同的多肽的序列。
130.如權(quán)利要求129所述的分離核酸,其特征在于,所述氨基酸序列與SEQID N0:7至 少90%相同。
131.如權(quán)利要求129所述的分離核酸,其特征在于,所述氨基酸序列與SEQID N0:7至 少95%相同。
132.—種分離核酸,其包含編碼氨基酸序列與SEQ ID NO :8至少85%相同的多肽的序列。
133.如權(quán)利要求132所述的分離核酸,其特征在于,所述氨基酸序列與SEQID N0:8至 少90%相同。
134.如權(quán)利要求132所述的分離核酸,其特征在于,所述氨基酸序列與SEQID N0:8至 少95%相同。
135.—種分離核酸,其包含編碼氨基酸序列與SEQ ID NO :9至少85%相同的多肽的序列。
136.如權(quán)利要求135所述的分離核酸,其特征在于,所述氨基酸序列與SEQID N0:9至 少90%相同。
137.如權(quán)利要求135所述的分離核酸,其特征在于,所述氨基酸序列與SEQID NO:9至 少95%相同。
138.—種分離核酸,其包含編碼氨基酸序列與選自下組的序列至少85%相同的多肽 的序歹丨J :SEQ ID NO 29 到 SEQ ID NO :1742。
139.如權(quán)利要求138所述的分離核酸,其特征在于,所述序列至少90%相同。
140.如權(quán)利要求138所述的分離核酸,其特征在于,所述序列至少95%相同。
141.如權(quán)利要求138所述的分離核酸,其特征在于,所述序列選自SEQIDN0:29到SEQ ID NO :1742 ο
142.—種誘導(dǎo)針對(duì)肺炎鏈球菌的免疫應(yīng)答的方法,所述方法包括給予對(duì)象有效量的肺 炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的LPXTG細(xì)胞壁錨定蛋白的免疫原性片段。
143.如權(quán)利要求142所述的方法,其特征在于,所述對(duì)象是人。
144.一種在細(xì)胞中表達(dá)針對(duì)肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛蛋白的抗體的 方法,所述方法包括在所述細(xì)胞中表達(dá)編碼針對(duì)肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛 蛋白的抗體的核酸。
145.如權(quán)利要求144所述的方法,其特征在于,所述菌毛蛋白是LPXTG細(xì)胞壁錨定蛋白。
146.一種誘導(dǎo)針對(duì)肺炎鏈球菌的免疫應(yīng)答的方法,所述方法包括給予對(duì)象有效量的編 碼如權(quán)利要求64所述多肽的核酸。
147.—種從包含肺炎鏈球菌的樣品純化肺炎鏈球菌的方法,所述方法包括a)提供包含結(jié)合有權(quán)利要求17所述抗體的固相載體的親和基質(zhì);b)使所述樣品與所述親和基質(zhì)相接觸,以形成親和基質(zhì)_肺炎鏈球菌復(fù)合物;c)將所述親和基質(zhì)-肺炎鏈球菌復(fù)合物與其余樣品分離;和d)從所述親和基質(zhì)釋放肺炎鏈球菌。
148.一種將細(xì)胞毒試劑或診斷試劑遞送至肺炎鏈球菌的方法,所述方法包括a)提供與權(quán)利要求17所述抗體或其片段偶聯(lián)的細(xì)胞毒試劑或診斷試劑;和b)使所述肺炎鏈球菌接觸所述抗體_試劑或片段_試劑偶聯(lián)物。
149.一種鑒定肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛的結(jié)合調(diào)節(jié)劑的方法,所述 方法包括使肺炎鏈球菌菌毛易于結(jié)合的動(dòng)物細(xì)胞與候選化合物和具有肺炎鏈球菌菌毛I(xiàn)I 島(INV104B)編碼菌毛的細(xì)菌細(xì)胞相接觸,和測(cè)定所述細(xì)菌細(xì)胞與所述動(dòng)物細(xì)胞的結(jié)合是 否受到抑制,其中,所述結(jié)合活性的抑制表明是肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛 的結(jié)合抑制劑。
150.一種鑒定肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼的菌毛活性的結(jié)合調(diào)節(jié)劑的方法, 所述方法包括使肺炎鏈球菌菌毛易于結(jié)合的細(xì)胞與候選化合物和肺炎鏈球菌菌毛I(xiàn)I島 (INV104B)編碼的菌毛相接觸;和測(cè)定所述菌毛與所述細(xì)胞的結(jié)合是否受到抑制,其中,所 述結(jié)合活性的抑制表明是肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛的結(jié)合抑制劑。
151.一種鑒定肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛的結(jié)合調(diào)節(jié)劑的方法,所述方法包括使肺炎鏈球菌菌毛易于結(jié)合的細(xì)胞與候選化合物和肺炎鏈球菌菌毛I(xiàn)I島 (INV104B)編碼的菌毛蛋白或其細(xì)胞結(jié)合片段相接觸;和測(cè)定所述菌毛蛋白或其細(xì)胞結(jié)合 片段與所述細(xì)胞的結(jié)合是否受到抑制,其中,所述結(jié)合活性的抑制表明是肺炎鏈球菌菌毛 II島(INV104B)編碼菌毛的結(jié)合抑制劑。
152.如權(quán)利要求151所述的方法,其特征在于,所述動(dòng)物細(xì)胞是分離或培養(yǎng)的。
153.—種分離肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛的方法,所述方法包括使產(chǎn)生肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛的肺炎鏈球菌細(xì)胞接受超聲處理或 分解酶消化;通過(guò)密度梯度離心分離非細(xì)胞組分;和 分離肺炎鏈球菌菌毛Π島(INV104B)編碼菌毛。
154.如權(quán)利要求153所述的方法,其特征在于,所述分解酶是變?nèi)芫亍?br>
155.如權(quán)利要求153所述的方法,其特征在于,采用密度梯度離心分離所述非細(xì)胞組分。
156.如權(quán)利要求153所述的方法,其特征在于,產(chǎn)生肺炎鏈球菌菌毛I(xiàn)I島(INV104B) 編碼菌毛的肺炎鏈球菌細(xì)胞是肺炎鏈球菌TIGR4細(xì)胞。
157.如權(quán)利要求153所述的方法,其特征在于,所述方法還包括用核酸酶降解核酸。
158.如權(quán)利要求153所述的方法,其特征在于,所述方法還包括通過(guò)以下方式降低多 分散性采用凝膠過(guò)濾色譜,根據(jù)大小分離肺炎鏈球菌菌毛I(xiàn)I島(INV104B)編碼菌毛。
全文摘要
描述了來(lái)自肺炎鏈球菌的多肽。在一些方面,所述多肽包括在肺炎鏈球菌分離物INV104中鑒定的來(lái)自第二菌毛島(菌毛I(xiàn)I島(INV104B))的菌毛多肽。在另一些方面,所述多肽包括肺炎鏈球菌分離物INV104中沒(méi)有的來(lái)自肺炎鏈球菌菌株23F、INV200和OXC141的菌毛多肽和非菌毛多肽。免疫原性組合物中可使用這些多肽及其片段和變體,以便預(yù)防性或治療性免疫對(duì)抗肺炎鏈球菌。也可以在用于產(chǎn)生抗體的組合物和免疫刺激物中使用這些多肽。還提供了抑制肺炎鏈球菌的方法、治療肺炎鏈球菌感染的方法、鑒定肺炎鏈球菌抑制劑的方法以及診斷/檢測(cè)肺炎鏈球菌感染的方法。
文檔編號(hào)C07K14/315GK101848929SQ200880100325
公開(kāi)日2010年9月29日 申請(qǐng)日期2008年5月23日 優(yōu)先權(quán)日2007年5月25日
發(fā)明者C·多納蒂, M·莫拉, M·莫斯切奧尼, V·馬西格納尼 申請(qǐng)人:諾華有限公司