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研究生:陳琪鈞
研究生(外文):Chi-Jene Chen
論文名稱:不同亞型之A型流行性感冒病毒PB1-F2蛋白之功能探討
論文名稱(外文):Functional study of influenza A virus PB1-F2 protein variants
指導教授:施信如施信如引用關係
指導教授(外文):Shin-Ru Shih
學位類別:碩士
校院名稱:長庚大學
系所名稱:醫學生物技術研究所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
中文關鍵詞:A型流行性感冒病毒粒線體標第序列
外文關鍵詞:Influenza A virusmitochondrial targeting sequencePB1-F2
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A型流感病毒具有八段負股RNA且至少可轉譯出十種病毒蛋白,然而第十一種病毒蛋白PB1-F2首次在A/Puerto Rico/8/34 (PR8)中發現,此蛋白由87個胺基酸組成且因具有粒線體標第序列可專一性地坐落至粒線體,藉影響粒線體膜電位通透性而造成細胞凋亡;分析台灣1995至2001年A型流感病毒卻發現H1N1與H3N2兩亞型具有不同胺基酸組成與長度之PB1-F2,因此在此兩種亞型中各選兩株病毒株,H1N1 PB1-F2胺基酸長度為90、57個,H3N2則為90、79個。因此我們觀察不同亞型PB1-F2其在細胞分布位置、對轉植感染細胞產生細胞凋亡能力,以及對病毒複製之影響。在共軛焦顯微鏡結果得知具有較多厭水性胺基酸之H1N1 90個胺基酸之PB1-F2與PR8相同可專一性坐落至粒線體,其他病毒株則是分布在整個細胞中;且所有病毒株均無法造成轉染細胞產生細胞凋亡現象,但有病毒存在之情況下卻發現H1N1 90個胺基酸之PB1-F2可加強caspase 3活化情形,H3N2 90個胺基酸之PB1-F2則無;在病毒複製過程中卻發現H3N2 90個胺基酸之PB1-F2具有增加病毒RNA數目能力,反觀H1N1 90個胺基酸之PB1-F2則無。由以上研究結果,不同亞型流感病毒PB1-F2似乎具有不同功能,此發現重要點即在於,一般認為流感病毒蛋白功能即使在不同亞型仍具有一致性的觀念是截然不同的。
Influenza A virus contains eight RNA segments and encodes 10 viral proteins. However, an 11th protein, called PB1-F2, was found in A/Puerto Rico/8/34 (H1N1). This novel protein is translated from an alternative open reading frame (ORF) in the PB1 gene. A significant fraction of PB1-F2 localize to the inner mitochondrial membrane in influenza A virus-infected cells. The mitochondrial targeting sequence (MTS) is predicted to form a positively charged amphipathic α-helix which is near the C terminus of PB1-F2 that is necessary for its inner mitochondrial localization. PB1-F2 appears to enhance virus-induced cell death by permeate and destabilize the mitochondrial membrane. The amino acid sequence and length of PB1-F2 in recent influenza A isolates are different from A/Puerto Rico/8/34 (H1N1). Therefore we selected two recent virus strains of H1N1 and H3N2 individually to study their mitochondrial localization and induced apoptosis in transfected cells. Only the PB1-F2 of H1N1 could localize to the mitochondrial as well as A/Puerto Rico/8/34. Neither H1N1 nor N3N2 PB1-F2 alone could trigger apoptosis in transfected MDCK cells. However, PB1-F2 of H1N1 but not PB1-F2 of H3N2 enhanced caspase 3 activation in transfected cells following virus infection. PB1-F2 of H3N2 increased virus replication in the tansfected MDCK cell which was infected with PB1-F2 deficient WSN recombinant virus, but the PB1-F2 of H1N1 did not cause this phenomenon.
目錄
指導教授推薦書……………………………………………………
論文口試委員會審定書……………………………………………
國科會授權書………………………………………………………iii
國家圖書館授權書…………………………………………………iv
長庚大學授權書……………………………………………………v
致謝…………………………………………………………………vi
中文摘要…………………………………………………………...vii
英文摘要 ………...………………………………………………..viii
第一章 簡介………...……………………………………………..1-6
第二章 研究目的……...……………………………………………7-8
第三章 實驗方法…………………………………………………..9-17
第四章 實驗結果………………………………………………….18-25
第五章 討論與未來方向…………………………………………..26-30
參考文獻 …………………………………………………………..31-35
附錄…………………………………………………………….…...65-70
1.Webster, R.G., W.J. Bean, O.T. Gorman, T.M. Chambers, and Y. Kawaoka, Evolution and ecology of influenza A viruses. Microbiol Rev, 1992. 56(1): p. 152-79.
2.Gibbs, M.J., J.S. Armstrong, and A.J. Gibbs, The haemagglutinin gene, but not the neuraminidase gene, of 'Spanish flu' was a recombinant. Philos Trans R Soc Lond B Biol Sci, 2001. 356(1416): p. 1845-55.
3.Fouchier, R.A., V. Munster, A. Wallensten, T.M. Bestebroer, S. Herfst, D. Smith, G.F. Rimmelzwaan, B. Olsen, and A.D. Osterhaus, Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol, 2005. 79(5): p. 2814-22.
4.Nakajima, K., [Influenza virus genome structure and encoded proteins]. Nippon Rinsho, 1997. 55(10): p. 2542-6.
5.Chen, W., P.A. Calvo, D. Malide, J. Gibbs, U. Schubert, I. Bacik, S. Basta, R. O'Neill, J. Schickli, P. Palese, P. Henklein, J.R. Bennink, and J.W. Yewdell, A novel influenza A virus mitochondrial protein that induces cell death. Nat Med, 2001. 7(12): p. 1306-12.
6.Gibbs, J.S., D. Malide, F. Hornung, J.R. Bennink, and J.W. Yewdell, The influenza A virus PB1-F2 protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function. J Virol, 2003. 77(13): p. 7214-24.
7.Pfanner, N., Protein sorting: recognizing mitochondrial presequences. Curr Biol, 2000. 10(11): p. R412-5.
8.Endo, T. and D. Kohda, Functions of outer membrane receptors in mitochondrial protein import. Biochim Biophys Acta, 2002. 1592(1): p. 3-14.
9.Brix, J., K. Dietmeier, and N. Pfanner, Differential recognition of preproteins by the purified cytosolic domains of the mitochondrial import receptors Tom20, Tom22, and Tom70. J Biol Chem, 1997. 272(33): p. 20730-5.
10.Chen, G.W., C.C. Yang, K.C. Tsao, C.G. Huang, L.A. Lee, W.Z. Yang, Y.L. Huang, T.Y. Lin, and S.R. Shih, Influenza A virus PB1-F2 gene in recent Taiwanese isolates. Emerg Infect Dis, 2004. 10(4): p. 630-6.
11.Boya, P., A.L. Pauleau, D. Poncet, R.A. Gonzalez-Polo, N. Zamzami, and G. Kroemer, Viral proteins targeting mitochondria: controlling cell death. Biochim Biophys Acta, 2004. 1659(2-3): p. 178-89.
12.D'Agostino, D.M., L. Zotti, T. Ferro, G. Franchini, L. Chieco-Bianchi, and V. Ciminale, The p13II protein of HTLV type 1: comparison with mitochondrial proteins coded by other human viruses. AIDS Res Hum Retroviruses, 2000. 16(16): p. 1765-70.
13.Derfuss, T., H. Fickenscher, M.S. Kraft, G. Henning, D. Lengenfelder, B. Fleckenstein, and E. Meinl, Antiapoptotic activity of the herpesvirus saimiri-encoded Bcl-2 homolog: stabilization of mitochondria and inhibition of caspase-3-like activity. J Virol, 1998. 72(7): p. 5897-904.
14.Cheng, E.H., J. Nicholas, D.S. Bellows, G.S. Hayward, H.G. Guo, M.S. Reitz, and J.M. Hardwick, A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc Natl Acad Sci U S A, 1997. 94(2): p. 690-4.
15.Bellows, D.S., B.N. Chau, P. Lee, Y. Lazebnik, W.H. Burns, and J.M. Hardwick, Antiapoptotic herpesvirus Bcl-2 homologs escape caspase-mediated conversion to proapoptotic proteins. J Virol, 2000. 74(11): p. 5024-31.
16.Vives, J., S. Juanola, J.J. Cairo, E. Prats, L. Cornudella, and F. Godia, Protective effect of viral homologues of bcl-2 on hybridoma cells under apoptosis-inducing conditions. Biotechnol Prog, 2003. 19(1): p. 84-9.
17.Bellows, D.S., M. Howell, C. Pearson, S.A. Hazlewood, and J.M. Hardwick, Epstein-Barr virus BALF1 is a BCL-2-like antagonist of the herpesvirus antiapoptotic BCL-2 proteins. J Virol, 2002. 76(5): p. 2469-79.
18.Kroemer, G., The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med, 1997. 3(6): p. 614-20.
19.Marshall, W.L., C. Yim, E. Gustafson, T. Graf, D.R. Sage, K. Hanify, L. Williams, J. Fingeroth, and R.W. Finberg, Epstein-Barr virus encodes a novel homolog of the bcl-2 oncogene that inhibits apoptosis and associates with Bax and Bak. J Virol, 1999. 73(6): p. 5181-5.
20.Colberg-Poley, A.M., M.B. Patel, D.P. Erezo, and J.E. Slater, Human cytomegalovirus UL37 immediate-early regulatory proteins traffic through the secretory apparatus and to mitochondria. J Gen Virol, 2000. 81(Pt 7): p. 1779-89.
21.Goldmacher, V.S., Cell death suppression by cytomegaloviruses. Apoptosis, 2005. 10(2): p. 251-65.
22.Andreau, K., M. Castedo, J.L. Perfettini, T. Roumier, E. Pichart, S. Souquere, S. Vivet, N. Larochette, and G. Kroemer, Preapoptotic chromatin condensation upstream of the mitochondrial checkpoint. J Biol Chem, 2004. 279(53): p. 55937-45.
23.Rahmani, Z., K.W. Huh, R. Lasher, and A. Siddiqui, Hepatitis B virus X protein colocalizes to mitochondria with a human voltage-dependent anion channel, HVDAC3, and alters its transmembrane potential. J Virol, 2000. 74(6): p. 2840-6.
24.Jacotot, E., L. Ravagnan, M. Loeffler, K.F. Ferri, H.L. Vieira, N. Zamzami, P. Costantini, S. Druillennec, J. Hoebeke, J.P. Briand, T. Irinopoulou, E. Daugas, S.A. Susin, D. Cointe, Z.H. Xie, J.C. Reed, B.P. Roques, and G. Kroemer, The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore. J Exp Med, 2000. 191(1): p. 33-46.
25.Ferguson, N.M., A.P. Galvani, and R.M. Bush, Ecological and immunological determinants of influenza evolution. Nature, 2003. 422(6930): p. 428-33.
26.Abed, Y., I. Hardy, Y. Li, and G. Boivin, Divergent evolution of hemagglutinin and neuraminidase genes in recent influenza A:H3N2 viruses isolated in Canada. J Med Virol, 2002. 67(4): p. 589-95.
27.Plotkin, J.B., J. Dushoff, and S.A. Levin, Hemagglutinin sequence clusters and the antigenic evolution of influenza A virus. Proc Natl Acad Sci U S A, 2002. 99(9): p. 6263-8.
28.Basler, C.F., X. Wang, E. Muhlberger, V. Volchkov, J. Paragas, H.D. Klenk, A. Garcia-Sastre, and P. Palese, The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc Natl Acad Sci U S A, 2000. 97(22): p. 12289-94.
29.Yamada, H., R. Chounan, Y. Higashi, N. Kurihara, and H. Kido, Mitochondrial targeting sequence of the influenza A virus PB1-F2 protein and its function in mitochondria. FEBS Lett, 2004. 578(3): p. 331-6.
30.Kurokawa, M., A.H. Koyama, S. Yasuoka, and A. Adachi, Influenza virus overcomes apoptosis by rapid multiplication. Int J Mol Med, 1999. 3(5): p. 527-30.
31.Chanturiya, A.N., G. Basanez, U. Schubert, P. Henklein, J.W. Yewdell, and J. Zimmerberg, PB1-F2, an influenza A virus-encoded proapoptotic mitochondrial protein, creates variably sized pores in planar lipid membranes. J Virol, 2004. 78(12): p. 6304-12.
32.Daugas, E., S.A. Susin, N. Zamzami, K.F. Ferri, T. Irinopoulou, N. Larochette, M.C. Prevost, B. Leber, D. Andrews, J. Penninger, and G. Kroemer, Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis. Faseb J, 2000. 14(5): p. 729-39.
33.Daugas, E., D. Nochy, L. Ravagnan, M. Loeffler, S.A. Susin, N. Zamzami, and G. Kroemer, Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis. FEBS Lett, 2000. 476(3): p. 118-23.
34.Thoulouze, M.I., M. Lafage, V.J. Yuste, G. Kroemer, S.A. Susin, N. Israel, and M. Lafon, Apoptosis inversely correlates with rabies virus neurotropism. Ann N Y Acad Sci, 2003. 1010: p. 598-603.
35.Wurzer, W.J., O. Planz, C. Ehrhardt, M. Giner, T. Silberzahn, S. Pleschka, and S. Ludwig, Caspase 3 activation is essential for efficient influenza virus propagation. Embo J, 2003. 22(11): p. 2717-28.
36.Julkunen, I., T. Sareneva, J. Pirhonen, T. Ronni, K. Melen, and S. Matikainen, Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression. Cytokine Growth Factor Rev, 2001. 12(2-3): p. 171-80.
37.Takizawa, T., C. Tatematsu, K. Ohashi, and Y. Nakanishi, Recruitment of apoptotic cysteine proteases (caspases) in influenza virus-induced cell death. Microbiol Immunol, 1999. 43(3): p. 245-52.
38.Hui, E.K., E.M. Yap, D.S. An, I.S. Chen, and D.P. Nayak, Inhibition of influenza virus matrix (M1) protein expression and virus replication by U6 promoter-driven and lentivirus-mediated delivery of siRNA. J Gen Virol, 2004. 85(Pt 7): p. 1877-84.
39.Liu, T. and Z. Ye, Restriction of viral replication by mutation of the influenza virus matrix protein. J Virol, 2002. 76(24): p. 13055-61.
40.Liu, W., H. Li, and Y.H. Chen, N-terminus of M2 protein could induce antibodies with inhibitory activity against influenza virus replication. FEMS Immunol Med Microbiol, 2003. 35(2): p. 141-6.
41.McCown, M.F. and A. Pekosz, The influenza A virus M2 cytoplasmic tail is required for infectious virus production and efficient genome packaging. J Virol, 2005. 79(6): p. 3595-605.
42.Portela, A. and P. Digard, The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. J Gen Virol, 2002. 83(Pt 4): p. 723-34.
43.Marion, R.M., T. Zurcher, S. de la Luna, and J. Ortin, Influenza virus NS1 protein interacts with viral transcription-replication complexes in vivo. J Gen Virol, 1997. 78 ( Pt 10): p. 2447-51.
44.Schultz-Cherry, S., N. Dybdahl-Sissoko, G. Neumann, Y. Kawaoka, and V.S. Hinshaw, Influenza virus ns1 protein induces apoptosis in cultured cells. J Virol, 2001. 75(17): p. 7875-81.
45.Zhirnov, O.P., T.E. Konakova, T. Wolff, and H.D. Klenk, NS1 protein of influenza A virus down-regulates apoptosis. J Virol, 2002. 76(4): p. 1617-25.
46.Zhirnov, O.P., T.E. Konakova, W. Garten, and H. Klenk, Caspase-dependent N-terminal cleavage of influenza virus nucleocapsid protein in infected cells. J Virol, 1999. 73(12): p. 10158-63.
47.Zhirnov, O.P., A.L. Ksenofontov, S.G. Kuzmina, and H.D. Klenk, Interaction of influenza A virus M1 matrix protein with caspases. Biochemistry (Mosc), 2002. 67(5): p. 534-9.
48.Ludwig, S., O. Planz, S. Pleschka, and T. Wolff, Influenza-virus-induced signaling cascades: targets for antiviral therapy? Trends Mol Med, 2003. 9(2): p. 46-52.
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