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研究生:謝明孝
研究生(外文):Ming-Shou Hsieh
論文名稱:H6N1禽流感病毒血球凝集素之Arg-201為病毒與宿主細胞結合之重要關鍵
論文名稱(外文):Arg-201 on hemagglutinin is required for H6N1 avian influenza virus to bind with host cells
指導教授:莊榮輝莊榮輝引用關係劉嚞睿
指導教授(外文):Rong-Huay JuangJe-Ruei Liu
口試委員:何杰龍張世宗王金和楊健志
口試委員(外文):Jie-Long HeShih-Chung ChangChing-Ho WangChien-Chih Yang
口試日期:2019-05-16
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2019
畢業學年度:107
語文別:中文
論文頁數:104
中文關鍵詞:禽流感病毒胺基酸電荷受體結合位兩階段結合模型
DOI:10.6342/NTU201900809
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本實驗室早先篩選得一株可辨認H6HA1禽流感病毒 (A/chicken/Taiwan/ 2838V/00) HA頭部序列的單株抗體EB2,並發現其抗原決定基上第二個鹼性胺基酸Arg-201 (R201) 受到HA1上N167之醣基所保護,可以抵抗來自胰蛋白酶之降解,以維持病毒的感染性。而R201位點之存在,於H6亞型的病毒中乃極度保守。為了探討此位點在感染機制上扮演的角色,我們發展了具有外泌功能的雙效型桿狀病毒表現系統,以表現具有醣基化的H6HA1樣本,與去除穿膜區接近全長的H6HA0樣本。此一表現質體使用GP67信號肽做為外泌序列,可將重組蛋白外泌至無血清培養基中以方便純化。在表現蛋白基因下游帶有共用mRNA之internal ribosome entry site 序列,可於胞內表現綠螢光蛋白質做為報導基因,做為表現蛋白質的偵測訊號。更使用此重組桿狀病毒感染斜紋夜盜蛾幼蟲,收集血淋巴之後,可以純化出醣基化之HA1蛋白質,並確認了此重組HA1具有單體與三聚體兩種形式。從細胞培養與蟲體表現之重組H6HA1可以誘發小鼠產生專一性抗H6亞型之抗血清,以做為次單位疫苗使用。所表現之H6HA1存在為三聚體形式,而H6HA0則只有單元體形式。H6HA1三聚體對胰蛋白酶水解具有較強抗性,但卻不能與胎球蛋白唾液酸受體結合。反之,單體H6HA0不具抵抗胰蛋白酶水解抗性,但卻可與胎球蛋白唾液酸受體結合。我們發現,鹼性胺基酸R201之正電荷對HA與宿主細胞唾液酸受體間的結合極為重要。HA0的R201A點突變重組蛋白,失去了對於胎球蛋白唾液酸受體的結合力。此外,HA與唾液酸受體的結合能力也受到環境pH值影響,也能被幾種帶電荷胺基酸抑制。根據以上觀察結果,我們提出了一種病毒與宿主細胞結合的兩階段模型。首先,流感病毒透過HA1上受體結合位,對宿主細胞表面之唾液酸受體進行專一性辨認,當病毒以胞飲進入入宿主細胞後,接著在胞內endosome的酸性環境下,HA三聚體頭部的R201正電荷可協助HA進行對細胞膜的錨定,並觸發後續的感染融合過程。
In our previous study, we produced a monoclonal antibody EB2 that recognized an epitope in the HA1 domain on the hemagglutinin (HA) of H6N1 influenza virus(A/chicken/Taiwan/2838V/00). The residue Arg-201 (R201) on this epitope was protected by the glycan at Asn-167 (N167) from tryptic digestion; therefore, the infectivity of the virus was retained. R201 was extremely conserved in various subtypes of the influenza virus. To explore the role of R201 and the protecting glycan, we developed a bi-cistronic baculovirus expression system for the production of H6HA1 and H6HA0 (nearly full-length HA), which were glycosylated in insect cells. In this construct, the GP67sp signal peptide promoted the secretion of the recombinant protein into the culture medium, and improved protein expression and purification. Enhanced green fluorescent protein, coexpressed through an internal ribosome entry site, served as a visible reporter for protein expression detection. The hemolymph of Spodoptera litura larvae infected with the bi-cistronic baculovirus was collected for the purification of the recombinant HA1, which was found to be glycosylated, and monomeric and trimeric forms of the recombinant HA1 were identified. Proteins expressed in both the cell culture and larvae served as effective subunit vaccines for the production of antiserum against HA. The antiserum recognized the H6 subtype of AIV but not the H5 subtype. The expressed H6HA1 was mostly found in the trimeric form, and the H6HA0 protein was only found in the monomeric form. The trimeric H6HA1 was resistant to tryptic digestion; however, it could not bind to fetuin, a glycoprotein containing sialylated N-linked and O-linked glycans. By contrast, the monomeric H6HA0 could bind to fetuin but was sensitive to tryptic digestion. We found that the positive charge on R201 was critical for binding HA to the negatively charged surface of host cells because the mutant R201A of H6HA0 lost its binding capacity substantially. Moreover, this binding capacity was dependent on the pH value and inhibited by free electrically charged amino acids. We propose a two-step model for binding the influenza virus with a host cell. The first step involved the specific recognition of the receptor binding site on HA to the sialylated glycan on the host cell. After the virus is engulfed by the acidic endosome, R201 could bind to the cell surface with stronger interactions and trigger the fusion process.
目 錄
致謝 i
目錄 ii
圖表目錄 v
中文摘要 vi
英文摘要 viii
第一章 緒論 1
1.1 禽流感的傳播歷史與起源 1
1.2 禽流感病毒 3
1.3 禽流感病毒的重要蛋白質 4
1.4 禽流感病毒的生活史 8
1.5 禽流感病毒對人類的潛在危險性 9
1.6 醣基化對於調控血球凝集素致病機制扮演重要角色 12
1.7 單株抗體工具 14
1.8 重組蛋白質表現系統 15
1.9 微生物表現系統 16
1.10 桿狀病毒-昆蟲細胞表現系統 17
1.11 研究動機及目的 20
第二章 材料與方法 23
2.1 病毒與抗原蛋白質定量 23
2.2 質體構築 23
2.3 膠體電泳 25
2.4 質體接合 25
2.5 轉型作用 25
2.6 以原核表現系統大量生產重組蛋白質 26
2.7 重組桿狀病毒的製備 27
2.8 重組桿狀病毒的純化 27
2.9 重組桿狀病毒的增殖、感染與力價標定 27
2.10 昆蟲細胞的貼附、懸浮培養與感染 28
2.11 以斜紋夜盜蛾幼蟲生產重組HA 28
2.12 HA結合唾液酸受體能力測試 29
第三章 結果與討論 30
3.1 建構具醣基化之雙效型外泌桿狀病毒表現系統 30
3.2 構築不同外泌之訊號肽比較其外泌效果 32
3.3 重組HA6HA1醣基化之確認與檢定 34
3.4 雙效型外泌桿狀病毒表現系統之表現與純化 36
3.5 利用斜紋夜盜蛾幼蟲生產重組H6HA1 39
3.6 自血淋巴中純化重組H6HA1 41
3.7 重組H6HA1誘導小鼠產生抗血清測試 43
3.8 H6HA1可組裝成三聚體與三聚體之抗trypsin水解保護效果 45
3.9 H6HA1上N167對於R201位點具有保護效果 48
3.10 帶正電荷之鹼性胺基酸R201位點可能參與HA1錨定SA受體 52
3.11 酸鹼值與游離胺基酸對於HA0與胎球蛋白受體結合的影響 56
3.12 流感病毒與宿主受體兩階段結合模型 58
第四章 未來研究方向 60
4.1 N167醣鏈對R201保護現象的延伸驗證 60
4.2 HA三聚體可能存在Tense form與Relax form兩種構形 60
4.3 使用Cyro-EM與smFRET驗證兩種構形 61
4.4 細胞免疫螢光染色觀察HA對宿主細胞受體之結合 62
4.5 深入探討RBS與R201在受體結合角色上之關聯性 62
4.6 撰寫適合比對搜尋病毒序列之專用程式 62
參考文獻 63
附錄A 生化實驗法 71
A.1 蛋白質電泳檢定法 71
A.2 單株抗體之製備 79
附錄B 相關補充數據資料 90
問答錄 99
參考文獻
Airenne, K.J., Hu, Y.-C., Kost, T.A., Smith, R.H., Kotin, R.M., Ono, C., Matsuura, Y., Wang, S. and Ylä-Herttuala, S. (2013) Baculovirus: an insect-derived vector for diverse gene transfer applications. Mol. Ther. 21, 739-49.
Alexander, D.J. (2007) An overview of the epidemiology of avian influenza. Vaccine 25, 5637-44.
Almond, J.W. (1977) A single gene determines the host range of influenza virus. Nature 270, 617-8.
Altmann, F., Staudacher, E., Wilson, I.B.H. and März, L. (1999) Insect cells as hosts for the expression of recombinant glycoproteins. Glycoconjugate J. 16, 109-23.
Bottcher, C., Ludwig, K., Herrmann, A., van Heel, M. and Stark, H. (1999) Structure of influenza haemagglutinin at neutral and at fusogenic pH by electron cryo-microscopy. FEBS Lett. 463, 255-9.
Bullough, P.A., Hughson, F.M., Skehel, J.J. and Wiley, D.C. (1994) Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 371, 37-43.
Carr, C.M. and Kim, P.S. (1994) Flu virus invasion: halfway there. Science 266, 234-6.
Cauldwell, A.V., Long, J.S., Moncorge, O. and Barclay, W.S. (2014) Viral determinants of influenza A virus host range. J. Gen. Virol. 95, 1193-210.
Chan, P.K. (2002) Outbreak of avian influenza A (H5N1) virus infection in Hong Kong in 1997. Clin. Infect. Dis. 34 Suppl 2, S58-64.
Chen, C.Y., Liu, H.J., Tsai, C.P., Chung, C.Y., Shih, Y.S., Chang, P.C., Chiu, Y.T. and Hu, Y.C. (2010) Baculovirus as an avian influenza vaccine vector: Differential immune responses elicited by different vector forms. Vaccine 28, 7644-51.
Chen, J.R., Ma, C. and Wong, C.H. (2011) Vaccine design of hemagglutinin glycoprotein against influenza. Trends Biotechnol. 29, 426-34.
Chen, Y.J., Chen, W.S. and Wu, T.Y. (2005) Development of a bi-cistronic baculovirus expression vector by the Rhopalosiphum padi virus 5'' internal ribosome entry site. Biochem. Biophys. Res. Commun. 335, 616-23.
Das, D.K., Govindan, R., Nikic-Spiegel, I., Krammer, F., Lemke, E.A. and Munro, J.B. (2018) Direct visualization of the conformational dynamics of single influenza hemagglutinin trimers. Cell 174, 926-37.
Das, K., Aramini, J.M., Ma, L.-C., Krug, R.M. and Arnold, E. (2010) Structures of influenza A proteins and insights into antiviral drug targets. Nat. Struct. Mol. Biol. 17, 530-8.
Deshpande, K.L., Fried, V.A., Ando, M. and Webster, R.G. (1987) Glycosylation affects cleavage of an H5N2 influenza virus hemagglutinin and regulates virulence. Proc. Natl. Acad. Sci. U. S. A. 84, 36-40.
Di Lella, S., Herrmann, A. and Mair, C.M. (2016) Modulation of the pH stability of influenza virus hemagglutinin: A host cell adaptation strategy. Biophys. J. 110, 2293-301.
Eckert, D.M. and Kim, P.S. (2001) Mechanisms of viral membrane fusion and its inhibition. Annu. Rev. Biochem. 70, 777-810.
Fera, A., Farrington, J.E., Zimmerberg, J. and Reese, T.S. (2012) A negative stain for electron microscopic tomography. Microsc. Microanal. 18, 331-5.
Fodor, E. (2013) The RNA polymerase of influenza a virus: mechanisms of viral transcription and replication. Acta. Virol. 57, 113-22.
Fontana, J. and Steven, A.C. (2013) At Low pH, influenza virus matrix protein M1 undergoes a conformational change prior to dissociating from the membrane. J. Virol. 87, 5621-8.
Gaidet, N., Dodman, T., Caron, A., Balança, G., Desvaux, S., Goutard, F., Cattoli, G., Lamarque, F., Hagemeijer, W. and Monicat, F. (2007) Avian influenza viruses in water birds, Africa. Emerg. Infect. Dis. 13, 626-9.
Galloway, S.E., Reed, M.L., Russell, C.J. and Steinhauer, D.A. (2013) Influenza HA subtypes demonstrate divergent phenotypes for cleavage activation and pH of fusion: implications for host range and adaptation. PLOS Pathog. 9, e1003151.
Gambaryan, A.S., Matrosovich, M.N., Bender, C.A. and Kilbourne, E.D. (1998) Differences in the biological phenotype of low-yielding (L) and high-yielding (H) variants of swine influenza virus A/NJ/11/76 are associated with their different receptor-binding activity. Virology 247, 223-31.
Gamblin, S.J. and Skehel, J.J. (2010) Influenza hemagglutinin and neuraminidase membrane glycoproteins. J. Biol. Chem. 285, 28403-9.
He, J.L., Chiu, Y.C., Chang, S.C., Wang, C.H. and Juang, R.H. (2015) Glycosylation at hemagglutinin Asn-167 protects the H6N1 avian influenza virus from tryptic cleavage at Arg-201 and maintains the viral infectivity. Virus Res. 197, 101-7.
He, J.L., Hsieh, M.S., Chiu, Y.C., Juang, R.H. and Wang, C.H. (2013) Preparation of monoclonal antibodies against poor immunogenic avian influenza virus proteins. J. Immunol. Methods 387, 43-50.
He, J.L., Hsieh, M.S., Juang, R.H. and Wang, C.H. (2014) A monoclonal antibody recognizes a highly conserved neutralizing epitope on hemagglutinin of H6N1 avian influenza virus. Vet. Microbiol. 174, 333-41.
Hensley, S.E., Das, S.R., Bailey, A.L., Schmidt, L.M., Hickman, H.D., Jayaraman, A., Viswanathan, K., Raman, R., Sasisekharan, R., Bennink, J.R. and Yewdell, J.W. (2009) Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift. Science 326, 734-8.
Holsinger, L.J., Nichani, D., Pinto, L.H. and Lamb, R.A. (1994) Influenza A virus M2 ion channel protein: a structure-function analysis. J. Virol. 68, 1551-63.
Hsieh, M.S., Chang, Y.C., He, J.L. and Juang, R.H. (2019) Positive charge of Arg-201 on hemagglutinin is required for the binding of H6N1 avian influenza virus to its target through a two-step process. Virus Res. 265, 132-7.
Hsieh, M.S., He, J.L., Wu, T.Y. and Juang, R.H. (2018) A secretory bi-cistronic baculovirus expression system with improved production of the HA1 protein of H6 influenza virus in insect cells and Spodoptera litura larvae. J Immunol. Methods 459, 81-9.
Hsieh, Y.C., Wu, T.Z., Liu, D.P., Shao, P.L., Chang, L.Y., Lu, C.Y., Lee, C.Y., Huang, F.Y. and Huang, L.M. (2006) Influenza pandemics: past, present and future. J. Formos. Med. Assoc. 105, 1-6.
Hsu, C.N. and Wang, C.H. (2006) Sequence comparison between two quasi strains of H6N1 with different pathogenicity from a single parental isolate. J. Microbiol. Immunol. Infect. 39, 292-6.
Huang, Q., Sivaramakrishna, R.P., Ludwig, K., Korte, T., Bottcher, C. and Herrmann, A. (2003) Early steps of the conformational change of influenza virus hemagglutinin to a fusion active state: stability and energetics of the hemagglutinin. Biochim. Biophys. Acta. 1614, 3-13.
Jadhao, S.J., Nguyen, D.C., Uyeki, T.M., Shaw, M., Maines, T., Rowe, T., Smith, C., Huynh, L.P., Nghiem, H.K., Nguyen, D.H., Nguyen, H.K., Nguyen, H.H., Hoang, L.T., Nguyen, T., Phuong, L.S., Klimov, A., Tumpey, T.M., Cox, N.J., Donis, R.O., Matsuoka, Y. and Katz, J.M. (2009) Genetic analysis of avian influenza A viruses isolated from domestic waterfowl in live-bird markets of Hanoi, Vietnam, preceding fatal H5N1 human infections in 2004. Arch. Virol. 154, 1249-61.
Jehle, J.A., Blissard, G.W., Bonning, B.C., Cory, J.S., Herniou, E.A., Rohrmann, G.F., Theilmann, D.A., Thiem, S.M. and Vlak, J.M. (2006) On the classification and nomenclature of baculoviruses: A proposal for revision. Arch. Virol. 151, 1257-66.
Jiang, L. and Eichelberger, M.C. (2015) Evaluation of Epic label-free technology to quantify functional recombinant hemagglutinin. Biol. Proced. Online 17, 7-15.
Jiang, L., Zhang, L., Ren, Q., Guo, Z., Kan, X., Yuan, J. and Yang, J. (2013) Origin and molecular characteristics of a novel 2013 avian influenza A (H6N1) virus causing human infection in Taiwan. Clin. Infect. Dis. 57, 1367-8.
Kato, T., Kajikawa, M., Maenaka, K. and Park, E.Y. (2010) Silkworm expression system as a platform technology in life science. Appl. Microbiol. Biotechnol. 85, 459-70.
Kilbourne, E.D. (2006) Influenza pandemics of the 20th century. Emerg. Infect .Dis. 12, 9-14.
Klemm, C., Boergeling, Y., Ludwig, S. and Ehrhardt, C. (2018) Immunomodulatory nonstructural proteins of influenza A viruses. Trends. Microbiol. 26, 624-36.
Kobayashi, Y. and Suzuki, Y. (2012) Compensatory evolution of net-charge in influenza A virus hemagglutinin. PLOS ONE 7, e40422-33.
Kohler, G. and Milstein, C. (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495-7.
Kost, T.A., Condreay, J.P. and Jarvis, D.L. (2005) Baculovirus as versatile vectors for protein expression in insect and mammalian cells. Nature biotech. 23, 567-75.
Lamb, R.A., Zebedee, S.L. and Richardson, C.D. (1985) Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface. Cell 40, 627-33.
Le, Q.M., Sakai-Tagawa, Y., Ozawa, M., Ito, M. and Kawaoka, Y. (2009) Selection of H5N1 influenza virus PB2 during replication in humans. J. Virol. 83, 5278-82.
Luczo, J.M., Tachedjian, M., Harper, J.A., Payne, J.S., Butler, J.M., Sapats, S.I., Lowther, S.L., Michalski, W.P., Stambas, J. and Bingham, J. (2018) Evolution of high pathogenicity of H5 avian influenza virus: haemagglutinin cleavage site selection of reverse-genetics mutants during passage in chickens. Sci. Rep. 8, 11518-31.
Lupiani, B. and Reddy, S.M. (2009) The history of avian influenza. Comp. Immunol .Microbiol. Infect. Dis. 32, 311-23.
Ma, W., Kahn, R.E. and Richt, J.A. (2008) The pig as a mixing vessel for influenza viruses: Human and veterinary implications. J. Mol. Genet. Med. 3, 158-66.
Margine, I., Palese, P. and Krammer, F. (2013) Expression of functional recombinant hemagglutinin and neuraminidase proteins from the novel H7N9 influenza virus using the baculovirus expression system. J. Vis. Exp., e51112-22.
McClellan, K. and Perry, C.M. (2001) Oseltamivir: a review of its use in influenza. Drugs 61, 263-83.
Moeller, A., Kirchdoerfer, R.N., Potter, C.S., Carragher, B. and Wilson, I.A. (2012) Organization of the influenza virus replication machinery. Science 338, 1631-4.
Mori, H., Nakazawa, H., Shirai, N., Shibata, N., Sumida, M. and Matsubara, F. (1992) Foreign gene expression by a baculovirus vector with an expanded host range. J. Gen. Virol. 73 ( Pt 7), 1877-80.
Naguib, M.M., Verhagen, J.H., Samy, A., Eriksson, P., Fife, M., Lundkvist, A., Ellstrom, P. and Jarhult, J.D. (2019) Avian influenza viruses at the wild-domestic bird interface in Egypt. Infect. Ecol. Epidemiol. 9.
Neumann, G. and Kawaoka, Y. (2006) Host range restriction and pathogenicity in the context of influenza pandemic. Emerg. Infect. Dis. 12, 881-6.
Neumann, G. and Kawaoka, Y. (2015) Transmission of influenza A viruses. Virology 479-480, 234-46.
Nguyen, D.C., Uyeki, T.M., Jadhao, S., Maines, T., Shaw, M., Matsuoka, Y., Smith, C., Rowe, T., Lu, X., Hall, H., Xu, X., Balish, A., Klimov, A., Tumpey, T.M., Swayne, D.E., Huynh, L.P., Nghiem, H.K., Nguyen, H.H., Hoang, L.T., Cox, N.J. and Katz, J.M. (2005) Isolation and characterization of avian influenza viruses, including highly pathogenic H5N1, from poultry in live bird markets in Hanoi, Vietnam, in 2001. J. Virol. 79, 4201-12.
Niles, W.D. and Cohen, F.S. (1991) The role of N-acetylneuraminic (sialic) acid in the pH dependence of influenza virion fusion with planar phospholipid membranes. J. Gen. Physiol. 97, 1121-40.
Ohuchi, R., Ohuchi, M., Garten, W. and Klenk, H.D. (1997) Oligosaccharides in the stem region maintain the influenza virus hemagglutinin in the metastable form required for fusion activity. J. Virol. 71, 3719-25.
Olsen, B., Munster, V.J., Wallensten, A., Waldenstrom, J., Osterhaus, A.D. and Fouchier, R.A. (2006) Global patterns of influenza a virus in wild birds. Science 312, 384-8.
Palomares, L.A., Realpe, M. and Ramírez, O.T. 2015 An overview of cell culture engineering for the insect cell-baculovirus expression vector system (BEVS). In: M. Al-Rubeai (Ed.) Animal Cell Culture. Springer International Publishing, Cham, p. 501-9.
Patterson Ross, Z., Komadina, N., Deng, Y.-M., Spirason, N., Kelly, H.A., Sullivan, S.G., Barr, I.G. and Holmes, E.C. (2015) Inter-seasonal influenza is characterized by extended virus transmission and persistence. PLOS Pathog.11, e1004991.
Rachakonda, P.S., Veit, M., Korte, T., Ludwig, K., Bottcher, C., Huang, Q., Schmidt, M.F. and Herrmann, A. (2007) The relevance of salt bridges for the stability of the influenza virus hemagglutinin. Faseb J. 21, 995-1002.
Rivkin, H., Kroemer, J.A., Bronshtein, A., Belausov, E., Webb, B.A. and Chejanovsky, N. (2006) Response of immunocompetent and immunosuppressed Spodoptera littoralis larvae to baculovirus infection. J. Gen. Virol. 87, 2217-25.
Rossman, J.S. and Lamb, R.A. (2011) Influenza virus assembly and budding. Virology 411, 229-36.
Royall, E., Woolaway, K.E., Schacherl, J., Kubick, S., Belsham, G.J. and Roberts, L.O. (2004) The Rhopalosiphum padi virus 5'' internal ribosome entry site is functional in Spodoptera frugiperda 21 cells and in their cell-free lysates: implications for the baculovirus expression system. J. Gen. Virol. 85, 1565-9.
Samji, T. (2009) Influenza A: understanding the viral life cycle. Yale J. Biol. Med. 82, 153-9.
Sarkar, T., Das, S., De, A., Nandy, P., Chattopadhyay, S., Chawla-Sarkar, M. and Nandy, A. (2015) H7N9 influenza outbreak in China 2013: In silico analyses of conserved segments of the hemagglutinin as a basis for the selection of peptide vaccine targets. Comput. Biol. Chem. 59 Pt A, 8-15.
Schäfer, W.(1955) Vergleichende sero-immunologische untersuchungen über die viren der influenza und klassischen geflügelpest. In: Zeitschrift für Naturforschung B, Vol. 10, p. 81-91.
Schulze, I.T. (1997) Effects of glycosylation on the properties and functions of influenza virus hemagglutinin. J. Infect. Dis. 176 Suppl 1, S24-8.
Senne, D.A., Panigrahy, B., Kawaoka, Y., Pearson, J.E., Suss, J., Lipkind, M., Kida, H. and Webster, R.G. (1996) Survey of the hemagglutinin (HA) cleavage site sequence of H5 and H7 avian influenza viruses: amino acid sequence at the HA cleavage site as a marker of pathogenicity potential. Avian Dis. 40, 425-37.
Sha, B. and Luo, M. (1997) Structure of a bifunctional membrane-RNA binding protein, influenza virus matrix protein M1. Nature Structural Biology 4, 239-44.
Shi, X. and Jarvis, D.L. (2007) Protein N-glycosylation in the baculovirus-insect cell system. Curr. drug targets 8, 1116-25.
Shih, A.C.C., Hsiao, T.C., Ho, M.S. and Li, W.H. (2007) Simultaneous amino acid substitutions at antigenic sites drive influenza A hemagglutinin evolution. Proc. Natl. Acad. Sci. U.S.A. 104, 6283-8.
Shimizu, K. (1997) Mechanisms of antigenic variation in influenza virus. Nihon Rinsho 55, 2610-6.
Shtyrya, Y.A., Mochalova, L.V. and Bovin, N.V. (2009) Influenza virus neuraminidase: structure and function. Acta nat. 1, 26-32.
Sims, L.D., Domenech, J., Benigno, C., Kahn, S., Kamata, A., Lubroth, J., Martin, V. and Roeder, P. (2005) Origin and evolution of highly pathogenic H5N1 avian influenza in Asia. Vet. Rec. 157, 159-64.
Sonnberg, S., Webby, R.J. and Webster, R.G. (2013) Natural history of highly pathogenic avian influenza H5N1. Virus Res. 178, 63-77.
Soundararajan, V., Tharakaraman, K., Raman, R., Raguram, S., Shriver, Z., Sasisekharan, V. and Sasisekharan, R. (2009) Extrapolating from sequence the 2009 H1N1 "swine" influenza virus. Nat. Biotechnol. 27, 510-3.
Subbarao, K., Klimov, A., Katz, J., Regnery, H., Lim, W., Hall, H., Perdue, M., Swayne, D., Bender, C., Huang, J., Hemphill, M., Rowe, T., Shaw, M., Xu, X., Fukuda, K. and Cox, N. (1998) Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 279, 393-6.
Takemoto, D.K., Skehel, J.J. and Wiley, D.C. (1996) A surface plasmon resonance assay for the binding of influenza virus hemagglutinin to its sialic acid receptor. Virology 217, 452-8.
Tate, M.D., Job, E.R., Deng, Y.-M., Gunalan, V., Maurer-Stroh, S. and Reading, P.C. (2014) Playing hide and seek: how glycosylation of the influenza virus hemagglutinin can modulate the immune response to infection. Viruses 6, 1294-316.
Tellier, R. (2006) Review of aerosol transmission of influenza A virus. Emerg. Infect. Dis. 12, 1657-62.
Tran, E.E., Podolsky, K.A., Bartesaghi, A., Kuybeda, O., Grandinetti, G., Wohlbold, T.J., Tan, G.S., Nachbagauer, R., Palese, P., Krammer, F. and Subramaniam, S. (2016) Cryo-electron microscopy structures of chimeric hemagglutinin displayed on a universal influenza vaccine candidate. MBio. 7, e00257-66.
Tuan, S.J., Li, N.J., Yeh, C.C., Tang, L.C. and Chi, H. (2014) Effects of green manure cover crops on Spodoptera litura (Lepidoptera: Noctuidae) populations. J. Econ. Entomol. 107, 897-905.
Underwood, P.A., Skehel, J.J. and Wiley, D.C. (1987) Receptor-binding characteristics of monoclonal antibody-selected antigenic variants of influenza virus. J. Virol. 61, 206-9.
van Oers, M.M., Pijlman, G.P. and Vlak, J.M. (2015) Thirty years of baculovirus-insect cell protein expression: from dark horse to mainstream technology. J. Gen. Virol. 96, 6-23.
Webster, D., Li, Y., Bastien, N., Garceau, R. and Hatchette, T.F. (2011) Oseltamivir-resistant pandemic H1N1 influenza. CMAJ. 183, 420-2.
Webster, R.G., Yakhno, M., Hinshaw, V.S., Bean, W.J. and Copal Murti, K. (1978) Intestinal influenza: Replication and characterization of influenza viruses in ducks. Virology 84, 268-78.
Whitford, M., Stewart, S., Kuzio, J. and Faulkner, P. (1989) Identification and sequence analysis of a gene encoding gp67, an abundant envelope glycoprotein of the baculovirus Autographa californica nuclear polyhedrosis virus. J. virol. 63, 1393-9.
Wiley, D.C. and Skehel, J.J. (1987) The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu. rev. Biochem. 56, 365-94.
Wiley, D.C., Wilson, I.A. and Skehel, J.J. (1981) Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289, 373-8.
Wilson, I.A., Skehel, J.J. and Wiley, D.C. (1981) Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 289, 366-73.
Worobey, M., Han, G.-Z. and Rambaut, A. (2014) Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus. Proc. Natl. Acad. Sci. U.S.A. 111, 8107-12.
Wu, T.Y., Chen, Y.J., Teng, C.Y., Chen, W.S. and Villaflores, O. (2012) A bi-cistronic baculovirus expression vector for improved recombinant protein production. Bioengineered bugs 3, 129-32.
Wu, Y.J., Teng, C.Y., Chen, Y.J., Chen, S.C., Chen, Y.J., Lin, Y.T. and Wu, T.Y. (2008) Internal ribosome entry site of Rhopalosiphum padi virus is functional in mammalian cells and has cryptic promoter activity in baculovirus-infected sf21 cells. Acta. Pharmacol. Sin. 29, 965-74.
Yang, H., Carney, P.J., Mishin, V.P., Guo, Z., Chang, J.C., Wentworth, D.E., Gubareva, L.V. and Stevens, J. (2016) Molecular characterizations of surface proteins hemagglutinin and neuraminidase from recent H5Nx avian influenza viruses. J. Virol. 90, 5770-84.
Yoshimura, A. and Ohnishi, S. (1984) Uncoating of influenza virus in endosomes. J. virol. 51, 497-504.
Yu, Y.G., King, D.S. and Shin, Y.K. (1994) Insertion of a coiled-coil peptide from influenza virus hemagglutinin into membranes. Science 266, 274-6.
Zheng, W. and Tao, Y.J. (2013) Structure and assembly of the influenza A virus ribonucleoprotein complex. FEBS Letters 587, 1206-14.
Zhou, N.N., Senne, D.A., Landgraf, J.S., Swenson, S.L., Erickson, G., Rossow, K., Liu, L., Yoon, K.j., Krauss, S. and Webster, R.G. (1999) Genetic reassortment of avian, swine, and human influenza A viruses in American pigs. J. virol. 73, 8851-6.
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