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標題: A型流感病毒RNA聚合酶抗體之製備與應用
Preparation and Application of the Antibodies against the Influenza A Virus RNA Polymerase
作者: 孫惠芬
Sun, Hui-Fen
關鍵字: influenza virus
RNA polymerase
出版社: 獸醫公共衛生學研究所
引用: Akarsu, H., Burmeister, W. P., Petosa, C., Petit, I., Muller, C. W., Ruigrok, R. W., and Baudin, F. (2003). Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2). EMBO J 22(18), 4646-55. Arzt, S., Petit, I., Burmeister, W. P., Ruigrok, R. W., and Baudin, F. (2004). Structure of a knockout mutant of influenza virus M1 protein that has altered activities in membrane binding, oligomerisation and binding to NEP (NS2). Virus Res 99(2), 115-9. Barcena, J., Ochoa, M., de la Luna, S., Melero, J. A., Nieto, A., Ortin, J., and Portela, A. (1994). Monoclonal antibodies against influenza virus PB2 and NP polypeptides interfere with the initiation step of viral mRNA synthesis in vitro. J Virol 68(11), 6900-9. Belakavadi, M., and Salimath, B. P. (2005). Mechanism of inhibition of ascites tumor growth in mice by curcumin is mediated by NF-kB and caspase activated DNase. Mol Cell Biochem 273(1-2), 57-67. Bethell, R. C., and Smith, P. W. (1997). Sialidase as a target for inhibitors of influenza virus replication. Expert Opin Investig Drugs 6(10), 1501-9. Bouloy, M., Morgan, M. A., Shatkin, A. J., and Krug, R. M. (1979). Cap and internal nucleotides of reovirus mRNA primers are incorporated into influenza viral complementary RNA during transcription in vitro. J Virol 32(3), 895-904. Bouloy, M., Plotch, S. J., and Krug, R. M. (1980). Both the 7-methyl and the 2''-O-methyl groups in the cap of mRNA strongly influence its ability to act as primer for influenza virus RNA transcription. Proc Natl Acad Sci U S A 77(7), 3952-6. Bouvier, N. M., and Palese, P. (2008). The biology of influenza viruses. Vaccine 26 Suppl 4, D49-53. Bui, H. H., Peters, B., Assarsson, E., Mbawuike, I., and Sette, A. (2007). Ab and T cell epitopes of influenza A virus, knowledge and opportunities. Proc Natl Acad Sci U S A 104(1), 246-51. Bui, M., Whittaker, G., and Helenius, A. (1996). Effect of M1 protein and low pH on nuclear transport of influenza virus ribonucleoproteins. J Virol 70(12), 8391-401. Chase, G., Deng, T., Fodor, E., Leung, B. W., Mayer, D., Schwemmle, M., and Brownlee, G. (2008). Hsp90 inhibitors reduce influenza virus replication in cell culture. Virology 377(2), 431-9. Chen, D.-Y. (2008). national chung hsing university, taichung. Cros, J. F., and Palese, P. (2003). Trafficking of viral genomic RNA into and out of the nucleus: influenza, Thogoto and Borna disease viruses. Virus Res 95(1-2), 3-12. Dalton, R. M., Mullin, A. E., Amorim, M. J., Medcalf, E., Tiley, L. S., and Digard, P. (2006). Temperature sensitive influenza A virus genome replication results from low thermal stability of polymerase-cRNA complexes. Virol J 3, 58. Deng, T., Engelhardt, O. G., Thomas, B., Akoulitchev, A. V., Brownlee, G. G., and Fodor, E. (2006). Role of ran binding protein 5 in nuclear import and assembly of the influenza virus RNA polymerase complex. J Virol 80(24), 11911-9. Deng, T., Sharps, J., Fodor, E., and Brownlee, G. G. (2005). In vitro assembly of PB2 with a PB1-PA dimer supports a new model of assembly of influenza A virus polymerase subunits into a functional trimeric complex. J Virol 79(13), 8669-74. Deng, T., Sharps, J. L., and Brownlee, G. G. (2006). Role of the influenza virus heterotrimeric RNA polymerase complex in the initiation of replication. J Gen Virol 87(Pt 11), 3373-7. Deng, T., Vreede, F. T., and Brownlee, G. G. (2006). Different de novo initiation strategies are used by influenza virus RNA polymerase on its cRNA and viral RNA promoters during viral RNA replication. J Virol 80(5), 2337-48. Dias, A., Bouvier, D., Crepin, T., McCarthy, A. A., Hart, D. J., Baudin, F., Cusack, S., and Ruigrok, R. W. (2009). The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 458(7240), 914-8. Digard, P., Elton, D., Bishop, K., Medcalf, E., Weeds, A., and Pope, B. (1999). Modulation of nuclear localization of the influenza virus nucleoprotein through interaction with actin filaments. J Virol 73(3), 2222-31. Elton, D., Simpson-Holley, M., Archer, K., Medcalf, L., Hallam, R., McCauley, J., and Digard, P. (2001). Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway. J Virol 75(1), 408-19. Fechter, P., Mingay, L., Sharps, J., Chambers, A., Fodor, E., and Brownlee, G. G. (2003). Two aromatic residues in the PB2 subunit of influenza A RNA polymerase are crucial for cap binding. J Biol Chem 278(22), 20381-8. Fodor, E., Crow, M., Mingay, L. J., Deng, T., Sharps, J., Fechter, P., and Brownlee, G. G. (2002). A single amino acid mutation in the PA subunit of the influenza virus RNA polymerase inhibits endonucleolytic cleavage of capped RNAs. J Virol 76(18), 8989-9001. Fodor, E., and Smith, M. (2004). The PA subunit is required for efficient nuclear accumulation of the PB1 subunit of the influenza A virus RNA polymerase complex. J Virol 78(17), 9144-53. Gabriel, G., Herwig, A., and Klenk, H. D. (2008). Interaction of polymerase subunit PB2 and NP with importin alpha1 is a determinant of host range of influenza A virus. PLoS Pathog 4(2), e11. Garcia-Sastre, A., Egorov, A., Matassov, D., Brandt, S., Levy, D. E., Durbin, J. E., Palese, P., and Muster, T. (1998). Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252(2), 324-30. Ghanem, A., Mayer, D., Chase, G., Tegge, W., Frank, R., Kochs, G., Garcia-Sastre, A., and Schwemmle, M. (2007). Peptide-mediated interference with influenza A virus polymerase. J Virol 81(14), 7801-4. Glaser, L., Conenello, G., Paulson, J., and Palese, P. (2007). Effective replication of human influenza viruses in mice lacking a major alpha2,6 sialyltransferase. Virus Res 126(1-2), 9-18. Glaser, L., Stevens, J., Zamarin, D., Wilson, I. A., Garcia-Sastre, A., Tumpey, T. M., Basler, C. F., Taubenberger, J. K., and Palese, P. (2005). A single amino acid substitution in 1918 influenza virus hemagglutinin changes receptor binding specificity. J Virol 79(17), 11533-6. Goto, H. (2004). [Novel function of plasminogen-binding activity of the NA determines the pathogenicity of influenza A virus]. Uirusu 54(1), 83-91. Hatta, M., Asano, Y., Masunaga, K., Ito, T., Okazaki, K., Toyoda, T., Kawaoka, Y., Ishihama, A., and Kida, H. (2000). Mapping of functional domains on the influenza A virus RNA polymerase PB2 molecule using monoclonal antibodies. Arch Virol 145(9), 1947-61. He, X., Zhou, J., Bartlam, M., Zhang, R., Ma, J., Lou, Z., Li, X., Li, J., Joachimiak, A., Zeng, Z., Ge, R., Rao, Z., and Liu, Y. (2008). Crystal structure of the polymerase PA(C)-PB1(N) complex from an avian influenza H5N1 virus. Nature 454(7208), 1123-6. Hemerka, J. N., Wang, D., Weng, Y., Lu, W., Kaushik, R. S., Jin, J., Harmon, A. F., and Li, F. (2009). Detection and characterization of influenza A virus PA-PB2 interaction through a bimolecular fluorescence complementation assay. J Virol 83(8), 3944-55. Honda, A., Mizumoto, K., and Ishihama, A. (1999). Two separate sequences of PB2 subunit constitute the RNA cap-binding site of influenza virus RNA polymerase. Genes Cells 4(8), 475-85. Honda, A., Mizumoto, K., and Ishihama, A. (2002). Minimum molecular architectures for transcription and replication of the influenza virus. Proc Natl Acad Sci U S A 99(20), 13166-71. Ishihama, A., Mizumoto, K., Kawakami, K., Kato, A., and Honda, A. (1986). Proofreading function associated with the RNA-dependent RNA polymerase from influenza virus. J Biol Chem 261(22), 10417-21. Ito, T., Suzuki, Y., Suzuki, T., Takada, A., Horimoto, T., Wells, K., Kida, H., Otsuki, K., Kiso, M., Ishida, H., and Kawaoka, Y. (2000). Recognition of N-glycolylneuraminic acid linked to galactose by the alpha2,3 linkage is associated with intestinal replication of influenza A virus in ducks. J Virol 74(19), 9300-5. Jing, X., Ma, C., Ohigashi, Y., Oliveira, F. A., Jardetzky, T. S., Pinto, L. H., and Lamb, R. A. (2008). Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel. Proc Natl Acad Sci U S A 105(31), 10967-72. Josset, L., Frobert, E., and Rosa-Calatrava, M. (2008). Influenza A replication and host nuclear compartments: many changes and many questions. J Clin Virol 43(4), 381-90. Kawaguchi, A., and Nagata, K. (2007). De novo replication of the influenza virus RNA genome is regulated by DNA replicative helicase, MCM. EMBO J 26(21), 4566-75. Kawaoka, Y., Krauss, S., and Webster, R. G. (1989). Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol 63(11), 4603-8. Kemler, I., Whittaker, G., and Helenius, A. (1994). Nuclear import of microinjected influenza virus ribonucleoproteins. Virology 202(2), 1028-33. Klumpp, K., Ruigrok, R. W., and Baudin, F. (1997). Roles of the influenza virus polymerase and nucleoprotein in forming a functional RNP structure. EMBO J 16(6), 1248-57. Kolpashchikov, D. M., Honda, A., and Ishihama, A. (2004). Structure-function relationship of the influenza virus RNA polymerase: primer-binding site on the PB1 subunit. Biochemistry 43(19), 5882-7. Krystal, M., Young, J. F., Palese, P., Wilson, I. A., Skehel, J. J., and Wiley, D. C. (1983). Sequential mutations in hemagglutinins of influenza B virus isolates: definition of antigenic domains. Proc Natl Acad Sci U S A 80(14), 4527-31. Li, C., Hatta, M., Watanabe, S., Neumann, G., and Kawaoka, Y. (2008). Compatibility among polymerase subunit proteins is a restricting factor in reassortment between equine H7N7 and human H3N2 influenza viruses. J Virol 82(23), 11880-8. Li, O. T., Chan, M. C., Leung, C. S., Chan, R. W., Guan, Y., Nicholls, J. M., and Poon, L. L. (2009). Full factorial analysis of Mammalian and avian influenza polymerase subunits suggests a role of an efficient polymerase for virus adaptation. PLoS ONE 4(5), e5658. Liao, R. S., Tomalty, L. L., Majury, A., and Zoutman, D. E. (2009). Comparison of viral isolation and multiplex real-time reverse transcription-PCR for confirmation of respiratory syncytial virus and influenza virus detection by antigen immunoassays. J Clin Microbiol 47(3), 527-32. Liu, D., Liu, X., Yan, J., Liu, W. J., and Gao, G. F. (2009a). Interspecies transmission and host restriction of avian H5N1 influenza virus. Sci China C Life Sci 52(5), 428-38. Liu, Y., Lou, Z., Bartlam, M., and Rao, Z. (2009b). Structure-function studies of the influenza virus RNA polymerase PA subunit. Sci China C Life Sci 52(5), 450-8. Luo, G. X., Luytjes, W., Enami, M., and Palese, P. (1991). The polyadenylation signal of influenza virus RNA involves a stretch of uridines followed by the RNA duplex of the panhandle structure. J Virol 65(6), 2861-7. Macken, C. A., Webby, R. J., and Bruno, W. J. (2006). Genotype turnover by reassortment of replication complex genes from avian influenza A virus. J Gen Virol 87(Pt 10), 2803-15. Mak, N. K., Leung, C. Y., Wei, X. Y., Shen, X. L., Wong, R. N., Leung, K. N., and Fung, M. C. (2004). Inhibition of RANTES expression by indirubin in influenza virus-infected human bronchial epithelial cells. Biochem Pharmacol 67(1), 167-74. Mark, G. E., Taylor, J. M., Broni, B., and Krug, R. M. (1979). Nuclear accumulation of influenza viral RNA transcripts and the effects of cycloheximide, actinomycin D, and alpha-amanitin. J Virol 29(2), 744-52. Mazur, I., Wurzer, W. J., Ehrhardt, C., Pleschka, S., Puthavathana, P., Silberzahn, T., Wolff, T., Planz, O., and Ludwig, S. (2007). Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-kappaB-inhibiting activity. Cell Microbiol 9(7), 1683-94. Melen, K., Fagerlund, R., Franke, J., Kohler, M., Kinnunen, L., and Julkunen, I. (2003). Importin alpha nuclear localization signal binding sites for STAT1, STAT2, and influenza A virus nucleoprotein. J Biol Chem 278(30), 28193-200. Melen, K., Kinnunen, L., Fagerlund, R., Ikonen, N., Twu, K. Y., Krug, R. M., and Julkunen, I. (2007). Nuclear and nucleolar targeting of influenza A virus NS1 protein: striking differences between different virus subtypes. J Virol 81(11), 5995-6006. Mena, I., Jambrina, E., Albo, C., Perales, B., Ortin, J., Arrese, M., Vallejo, D., and Portela, A. (1999). Mutational analysis of influenza A virus nucleoprotein: identification of mutations that affect RNA replication. J Virol 73(2), 1186-94. Mikulasova, A., Vareckova, E., and Fodor, E. (2000). Transcription and replication of the influenza a virus genome. Acta Virol 44(5), 273-82. Momose, F., Basler, C. F., O''Neill, R. E., Iwamatsu, A., Palese, P., and Nagata, K. (2001). Cellular splicing factor RAF-2p48/NPI-5/BAT1/UAP56 interacts with the influenza virus nucleoprotein and enhances viral RNA synthesis. J Virol 75(4), 1899-908. Momose, F., Naito, T., Yano, K., Sugimoto, S., Morikawa, Y., and Nagata, K. (2002). Identification of Hsp90 as a stimulatory host factor involved in influenza virus RNA synthesis. J Biol Chem 277(47), 45306-14. Mukhtar, M. M., Li, S., Li, W., Wan, T., Mu, Y., Wei, W., Kang, L., Rasool, S. T., Xiao, Y., Zhu, Y., and Wu, J. (2009). Single-chain intracellular antibodies inhibit influenza virus replication by disrupting interaction of proteins involved in viral replication and transcription. Int J Biochem Cell Biol 41(3), 554-60. Mullin, A. E., Dalton, R. M., Amorim, M. J., Elton, D., and Digard, P. (2004). Increased amounts of the influenza virus nucleoprotein do not promote higher levels of viral genome replication. J Gen Virol 85(Pt 12), 3689-98. Naffakh, N., Tomoiu, A., Rameix-Welti, M. A., and van der Werf, S. (2008). Host restriction of avian influenza viruses at the level of the ribonucleoproteins. Annu Rev Microbiol 62, 403-24. Nagata, K., Kawaguchi, A., and Naito, T. (2008). Host factors for replication and transcription of the influenza virus genome. Rev Med Virol 18(4), 247-60. Naito, T., Momose, F., Kawaguchi, A., and Nagata, K. (2007). Involvement of Hsp90 in assembly and nuclear import of influenza virus RNA polymerase subunits. J Virol 81(3), 1339-49. Nakagawa, Y., Oda, K., and Nakada, S. (1996). The PB1 subunit alone can catalyze cRNA synthesis, and the PA subunit in addition to the PB1 subunit is required for viral RNA synthesis in replication of the influenza virus genome. J Virol 70(9), 6390-4. Nayak, D. P., Balogun, R. A., Yamada, H., Zhou, Z. H., and Barman, S. (2009). Influenza virus morphogenesis and budding. Virus Res. Nedyalkova, M. S., Hayden, F. G., Webster, R. G., and Gubareva, L. V. (2002). Accumulation of defective neuraminidase (NA) genes by influenza A viruses in the presence of NA inhibitors as a marker of reduced dependence on NA. J Infect Dis 185(5), 591-8. Neumann, G., Castrucci, M. R., and Kawaoka, Y. (1997). Nuclear import and export of influenza virus nucleoprotein. J Virol 71(12), 9690-700. Newcomb, L. L., Kuo, R. L., Ye, Q., Jiang, Y., Tao, Y. J., and Krug, R. M. (2009). Interaction of the influenza a virus nucleocapsid protein with the viral RNA polymerase potentiates unprimed viral RNA replication. J Virol 83(1), 29-36. Nieto, A., de la Luna, S., Barcena, J., Portela, A., and Ortin, J. (1994). Complex structure of the nuclear translocation signal of influenza virus polymerase PA subunit. J Gen Virol 75 ( Pt 1), 29-36. Nieto, A., de la Luna, S., Barcena, J., Portela, A., Valcarcel, J., Melero, J. A., and Ortin, J. (1992). Nuclear transport of influenza virus polymerase PA protein. Virus Res 24(1), 65-75. O''Neill, R. E., Talon, J., and Palese, P. (1998). The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins. EMBO J 17(1), 288-96. Ochoa, M., Barcena, J., de la Luna, S., Melero, J. A., Douglas, A. R., Nieto, A., Ortin, J., Skehel, J. J., and Portela, A. (1995). Epitope mapping of cross-reactive monoclonal antibodies specific for the influenza A virus PA and PB2 polypeptides. Virus Res 37(3), 305-15. Osterholm, M. T. (2005). Preparing for the next pandemic. N Engl J Med 352(18), 1839-42. Ozawa, M., Fujii, K., Muramoto, Y., Yamada, S., Yamayoshi, S., Takada, A., Goto, H., Horimoto, T., and Kawaoka, Y. (2007). Contributions of two nuclear localization signals of influenza A virus nucleoprotein to viral replication. J Virol 81(1), 30-41. Palese, P. (1977). The genes of influenza virus. Cell 10(1), 1-10. Perales, B., Sanz-Ezquerro, J. J., Gastaminza, P., Ortega, J., Santaren, J. F., Ortin, J., and Nieto, A. (2000). The replication activity of influenza virus polymerase is linked to the capacity of the PA subunit to induce proteolysis. J Virol 74(3), 1307-12. Pielak, R. M., Schnell, J. R., and Chou, J. J. (2009). Mechanism of drug inhibition and drug resistance of influenza A M2 channel. Proc Natl Acad Sci U S A 106(18), 7379-84. Plotch, S. J., Bouloy, M., Ulmanen, I., and Krug, R. M. (1981). A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell 23(3), 847-58. Plotch, S. J., O''Hara, B., Morin, J., Palant, O., LaRocque, J., Bloom, J. D., Lang, S. A., Jr., DiGrandi, M. J., Bradley, M., Nilakantan, R., and Gluzman, Y. (1999). Inhibition of influenza A virus replication by compounds interfering with the fusogenic function of the viral hemagglutinin. J Virol 73(1), 140-51. Poole, E. L., Medcalf, L., Elton, D., and Digard, P. (2007). Evidence that the C-terminal PB2-binding region of the influenza A virus PB1 protein is a discrete alpha-helical domain. FEBS Lett 581(27), 5300-6. Portela, A., and Digard, P. (2002). The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. J Gen Virol 83(Pt 4), 723-34. Pritlove, D. C., Poon, L. L., Fodor, E., Sharps, J., and Brownlee, G. G. (1998). Polyadenylation of influenza virus mRNA transcribed in vitro from model virion RNA templates: requirement for 5'' conserved sequences. J Virol 72(2), 1280-6. Qiu, Y., and Krug, R. M. (1994). The influenza virus NS1 protein is a poly(A)-binding protein that inhibits nuclear export of mRNAs containing poly(A). J Virol 68(4), 2425-32. Resa-Infante, P., Jorba, N., Zamarreno, N., Fernandez, Y., Juarez, S., and Ortin, J. (2008). The host-dependent interaction of alpha-importins with influenza PB2 polymerase subunit is required for virus RNA replication. PLoS ONE 3(12), e3904. Rudneva, I. A., Kovaleva, V. P., Varich, N. L., Farashyan, V. R., Gubareva, L. V., Yamnikova, S. S., Popova, I. A., Presnova, V. P., and Kaverin, N. V. (1993). Influenza A virus reassortants with surface glycoprotein genes of the avian parent viruses: effects of HA and NA gene combinations on virus aggregation. Arch Virol 133(3-4), 437-50. Ruigrok, R. W., Barge, A., Durrer, P., Brunner, J., Ma, K., and Whittaker, G. R. (2000). Membrane interaction of influenza virus M1 protein. Virology 267(2), 289-98. Ryan, D. M., Ticehurst, J., Dempsey, M. H., and Penn, C. R. (1994). Inhibition of influenza virus replication in mice by GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid) is consistent with extracellular activity of viral neuraminidase (sialidase). Antimicrob Agents Chemother 38(10), 2270-5. Schnell, J. R., and Chou, J. J. (2008). Structure and mechanism of the M2 proton channel of influenza A virus. Nature 451(7178), 591-5. Shapiro, G. I., Gurney, T., Jr., and Krug, R. M. (1987). Influenza virus gene expression: control mechanisms at early and late times of infection and nuclear-cytoplasmic transport of virus-specific RNAs. J Virol 61(3), 764-73. Shaw, M. L., Stone, K. L., Colangelo, C. M., Gulcicek, E. E., and Palese, P. (2008). Cellular proteins in influenza virus particles. PLoS Pathog 4(6), e1000085. Shih, S. R., Nemeroff, M. E., and Krug, R. M. (1995). The choice of alternative 5'' splice sites in influenza virus M1 mRNA is regulated by the viral polymerase complex. Proc Natl Acad Sci U S A 92(14), 6324-8. Shinya, K. (2008). Host adaptation mechanisms of Influenza A viruses. Uirusu 58(1), 69-72. Skorko, R., Summers, D. F., and Galarza, J. M. (1991). Influenza A virus in vitro transcription: roles of NS1 and NP proteins in regulating RNA synthesis. Virology 180(2), 668-77. Stambas, J., Guillonneau, C., Kedzierska, K., Mintern, J. D., Doherty, P. C., and La Gruta, N. L. (2008). Killer T cells in influenza. Pharmacol Ther 120(2), 186-96. Suzuki, T., Takahashi, T., Guo, C. T., Hidari, K. I., Miyamoto, D., Goto, H., Kawaoka, Y., and Suzuki, Y. (2005). Sialidase activity of influenza A virus in an endocytic pathway enhances viral replication. J Virol 79(18), 11705-15. Tarendeau, F., Boudet, J., Guilligay, D., Mas, P. J., Bougault, C. M., Boulo, S., Baudin, F., Ruigrok, R. W., Daigle, N., Ellenberg, J., Cusack, S., Simorre, J. P., and Hart, D. J. (2007). Structure and nuclear import function of the C-terminal domain of influenza virus polymerase PB2 subunit. Nat Struct Mol Biol 14(3), 229-33. Taylor, J. M., Illmensee, R., Litwin, S., Herring, L., Broni, B., and Krug, R. M. (1977). Use of specific radioactive probes to study transcription and replication of the influenza virus genome. J Virol 21(2), 530-40. Trushinskaya, G. N., Ivanova, V. T., and Zakstelskaya, L. (1984). Detection of influenza virus by means of immune sera to M and RNP inner proteins in solid phase radioimmunoassay. Acta Virol 28(6), 487-94. Urabe, M., Tanaka, T., Odagiri, T., Tashiro, M., and Tobita, K. (1993). Persistence of viral genes in a variant of MDBK cell after productive replication of a mutant of influenza virus A/WSN. Arch Virol 128(1-2), 97-110. Valcarcel, J., Portela, A., and Ortin, J. (1991). Regulated M1 mRNA splicing in influenza virus-infected cells. J Gen Virol 72 ( Pt 6), 1301-8. Venkatramani, L., Bochkareva, E., Lee, J. T., Gulati, U., Graeme Laver, W., Bochkarev, A., and Air, G. M. (2006). An epidemiologically significant epitope of a 1998 human influenza virus neuraminidase forms a highly hydrated interface in the NA-antibody complex. J Mol Biol 356(3), 651-63. Vreede, F. T., and Brownlee, G. G. (2007). Influenza virion-derived viral ribonucleoproteins synthesize both mRNA and cRNA in vitro. J Virol 81(5), 2196-204. Vreede, F. T., Jung, T. E., and Brownlee, G. G. (2004). Model suggesting that replication of influenza virus is regulated by stabilization of replicative intermediates. J Virol 78(17), 9568-72. Wang, P., Song, W., Mok, B. W., Zhao, P., Qin, K., Lai, A., Smith, G. J., Zhang, J., Lin, T., Guan, Y., and Chen, H. (2009). Nuclear factor 90, NF90, negatively regulates influenza virus replication by interacting with viral nucleoprotein. J Virol. Wasilenko, J. L., Lee, C. W., Sarmento, L., Spackman, E., Kapczynski, D. R., Suarez, D. L., and Pantin-Jackwood, M. J. (2008). NP, PB1, and PB2 viral genes contribute to altered replication of H5N1 avian influenza viruses in chickens. J Virol 82(9), 4544-53. World Health Organization. Dept. of Immunization Vaccines and Biologicals. (2009). "Global pandemic influenza action plan to increase vaccine supply : progress report 2008." World Health Organization, Geneva. Wu, W. W., Sun, Y. H., and Pante, N. (2007). Nuclear import of influenza A viral ribonucleoprotein complexes is mediated by two nuclear localization sequences on viral nucleoprotein. Virol J 4, 49. Wurzer, W. J., Planz, O., Ehrhardt, C., Giner, M., Silberzahn, T., Pleschka, S., and Ludwig, S. (2003). Caspase 3 activation is essential for efficient influenza virus propagation. EMBO J 22(11), 2717-28. Xu, Y. X., Pindolia, K. R., Janakiraman, N., Chapman, R. A., and Gautam, S. C. (1997). Curcumin inhibits IL1 alpha and TNF-alpha induction of AP-1 and NF-kB DNA-binding activity in bone marrow stromal cells. Hematopathol Mol Hematol 11(1), 49-62. Zheng, H., Palese, P., and Garcia-Sastre, A. (1996). Nonconserved nucleotides at the 3'' and 5'' ends of an influenza A virus RNA play an important role in viral RNA replication. Virology 217(1), 242-51.
摘要: 流感病毒RNA聚合酶(簡稱RdRp)由三種病毒次單位聚合酶蛋白組成:PA、PB1、PB2,為轉錄及複製所必須,突顯出在抗病毒機制上的重要性。為了了解流感病毒聚合酶的相關機制,抗體是最常用來分析的重要工具。本實驗利用原核系統表現重組流感病毒(A/ Puerto Rico/ 8/ 34)RdRp親水性氨基酸,重組蛋白質以鎳離子螯合管柱純化,經定量後進行動物接種,最後獲得不同動物來源的抗體: rabbit anti-PA、 chicken anti-PB1、 mouse anti-PB2。使用免疫轉漬法確認抗體對流感病毒H1N1、H6N1,聚合酶具有專一性外,也可辨識桿狀病毒系統(baculovirus system)表現的流感病毒聚合酶次單位蛋白,相同的結果亦在間接免疫螢光分析中可見。另外使用protein A agarose成功地純化不同抗體樣本中的IgG分子。後續運用多種免疫分析方法檢視抗流感病毒藥物:薑黃素(curcumin)與薑辣素([6]-gingerol),在間接免疫螢光分析觀察到薑黃素的作用在阻礙了流感病毒對細胞的感染,而薑辣素則無此作用,但對病毒蛋白質的合成具有降低的趨勢,因此兩者藥物是以不同方式達到抑制流感病毒的增殖。最後藉由商品化試劑包覆rabbit anti-PA IgG分子形成脂質複合體,運送抗體進入細胞質,以間接免疫螢光分析比較細胞對病毒感染情形,在帶有抗體分子的細胞中,病毒蛋白質的生成減少,初步證實以抑制流感病毒聚合酶功能的抗病毒策略具有可行性。未來以人類與動物體應用原則下,期許以流感病毒為主體的virosome形式包覆有效抑制流感病毒聚合酶的物質,直接在呼吸道對病毒發揮屏障作用,以這樣的方式達到預防與治療的雙重效果。
Influenza virus RNA polymerase (RdRP) containing three subunits: PA, PB1, PB2, is required for transcription and replication of viral RNA that has become a promising target for developing an alternative anti-viral agent. The antibodies were the most useful tools for study the influenza RdRp interaction. Recombinant three subunits RdRP of influenza virus (A/Puerto Rico/8/34) were expressed in prokaryotic system and were then used as antigens to produce antibodies from different animals: rabbit anti-PA, chicken anti-PB1, mouse anti-PB2. Consistent results were obtained from the immunoblot and indirected immunofluorescence assays: these antibodies were able to specifically recognize both the influenza A viruses polymerase from H1N1 or H6N1 infected and baculovirus system expressed. The IgG molecule was successfully purified through protein A agarose. Subsequently, application of such antibodies in study of the mechanism of anti-viral agents, curcumin and [6]-gingerol, the indirected immunofluorescence assays revealed that both chemicals reduced the viral replication via different mechanisms: curcumin interferenced the infection rate of influenza virus but [6]-gingerol didn't. Finally, the intracellular delivered with lipoplex, the complex of commercial reagent and rabbit anti-PA IgG, that appeared to reduce influenza viral protein synthesis. Hence, antibodies against viral RdRp may serve as an alternative therapeutic target for influenza virus infection. We expected that extend combination the influenza virosome and RdRp antagonist to set up the immuno-barrier of the respiratory tract by nasal admission. By this rule for human and animal to achieve prevent and therapeutic effect.
其他識別: U0005-2707200920373000
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