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Interferon Antagonists of Influenza Viruses

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Book cover Modulation of Host Gene Expression and Innate Immunity by Viruses

8. Conclusions

Although our understanding on how influenza and Thogoto viruses inhibit the IFN response has greatly increased in the last years, there are still many interesting unanswered questions in this field. It will be important to determine the precise mechanisms of action of the NS1 and ML proteins of these viruses, as well as their contribution to host and tissue tropism and to virulence. Research in this area also requires a better knowledge on the cell processes that result in activation of the IFN system and in the induction of the IFN-mediated antiviral state. In addition, development of vaccines and antivirals against influenza virus might be possible by targeting the NS1 protein. If successful, these approaches would also represent a proof-of-concept that can be applied to many other viruses known to contain IFN antagonist genes.

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References

  1. Thompson, W.W., Shay, D.K., Weintraub, E., Brammer, L., Cox, N., Anderson, L.J. & Fukuda, K., 2003, Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 289:179–186

    PubMed  Google Scholar 

  2. Webster, R.G., Bean, W.J., Gorman, O.T., Chambers, T.M. & Kawaoka, Y., 1992, Evolution and ecology of influenza A viruses. Microbiol. Rev. 56:152–179

    PubMed  CAS  Google Scholar 

  3. Palese, P., 1977, The genes of influenza virus. Cell 10:1–10

    PubMed  CAS  Google Scholar 

  4. Lamb, R.A. & Krug, R.M., 2001. In Fields Virology (Knipe, D.M. et al. eds.) Lippincott-Raven, Philadelphia, pp1487–1531.

    Google Scholar 

  5. Pinto, L.H., Holsinger, L.J. & Lamb, R.A., 1992, Influenza virus M2 protein has ion channel activity. Cell 69:517–528

    PubMed  CAS  Google Scholar 

  6. Mould, J.A., Paterson, R.G., Takeda, M., Ohigashi, Y., Venkataraman, P., Lamb, R.A. & Pinto, L.H., 2003, Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes. Dev. Cell. 5:175–184

    PubMed  CAS  Google Scholar 

  7. Hongo, S., Ishii, K., Mori, K., Takashita, E., Muraki, Y., Matsuzaki, Y. & Sugawara, K., 2004, Detection of ion channel activity in Xenopus laevis oocytes expressing Influenza C virus CM2 protein. Arch. Virol. 149:35–50

    PubMed  CAS  Google Scholar 

  8. Chen, W., Calvo, P.A., Malide, D., Gibbs, J., Schubert, U., Bacik, I., Basta, S., O’Neill, R., Schickli, J., Palese, P., Henklein, P., Bennink, J.R. & Yewdell, J.W., 2001, A novel influenza A virus mitochondrial protein that induces cell death. Nat. Med. 7:1306–1312

    PubMed  CAS  Google Scholar 

  9. Paragas, J., Talon, J., O’Neill, R.E., Anderson, D.K., García-Sastre, A. & Palese, P., 2001, Influenza B and C virus NEP (NS2) proteins possess nuclear export activities. J. Virol. 75:7375–7383

    PubMed  CAS  Google Scholar 

  10. Wathelet, M.G., Lin, C.H., Parekh, B.S., Ronco, L.V., Howley, P.M. & Maniatis, T., 1998, Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol. Cell 1:507–518

    PubMed  CAS  Google Scholar 

  11. Sato, M., Tanaka, N., Hata, N., Oda, E. & Taniguchi, T., 1998, Involvement of the IRF family transcription factor IRF-3 in virus-induced activation of the IFN-ß gene. FEBS Lett. 425:112–116

    PubMed  CAS  Google Scholar 

  12. Juang, Y., Lowther, W., Kellum, M., Au, W.C., Lin, R., Hiscott, J. & Pitha, P.M., 1998, Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3. Proc. Natl. Acad. Sci. (USA) 95:9837–9842

    CAS  Google Scholar 

  13. Yoneyama, M., Suhara, W., Fukuhara, Y., Fukuda, M., Nishida, E. & Fujita, T., 1998, Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300. EMBO J. 17:1087–1095

    PubMed  CAS  Google Scholar 

  14. Weaver, B.K., Kumar, K.P. & Reich, N.C., 1998, Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1. Mol. Cell. Biol. 18:1359–1368

    PubMed  CAS  Google Scholar 

  15. Sharma, S., TenOever, B.R., Grandvaux, N., Zhou, G.P., Lin, R. & Hiscott, J., 2003, Triggering the interferon antiviral response through an IKK-related pathway. Science 300:1148–1151

    PubMed  CAS  Google Scholar 

  16. Fitzgerald, K.A., McWhirter, S.M., Faia, K.L., Rowe, D.C., Latz, E., Golenbock, D.T., Coyle, A.J., Liao, S.M. & Maniatis, T., 2003, IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat. Immunol. 4:491–496

    PubMed  CAS  Google Scholar 

  17. Der, S.D., Zhou, A., Williams, B.R. & Silverman, R.H., 1998, Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc. Natl. Acad. Sci. (USA) 95:15623–15628

    CAS  Google Scholar 

  18. García-Sastre, A., Durbin, R.K., Zheng, H., Palese, P., Gertner, R., Levy, D.E. & Durbin, J.E., 1998, The role of interferon in the tropism of influenza virus. J. Virol. 72:8550–8558

    PubMed  Google Scholar 

  19. Durbin, J.E., Fernandez-Sesma, A., Lee, C.K., Rao, T.D., Frey, A.B., Moran, T.M., Vukmanovic, S., García-Sastre, A. & Levy, D.E., 2000, Type I IFN modulates innate and specific antiviral immunity. J. Immunol. 164:4220–4228

    PubMed  CAS  Google Scholar 

  20. Pasare, C. & Medzhitov, R., 2004, Toll-like receptors and acquired immunity. Semin. Immunol. 16:23–26

    PubMed  CAS  Google Scholar 

  21. Akira, S. & Takeda, K., 2004, Toll-like receptor signalling. Nat. Rev. Immunol. 4:499–511

    PubMed  CAS  Google Scholar 

  22. Bieback, K., Lien, E., Klagge, I.M., Avota, E., Schneider-Schaulies, J., Duprex, W.P., Wagner, H., Kirschning, C.J., Ter Meulen, V. & Schneider-Schaulies, S., 2002, Hemagglutinin protein of wild-type measles virus activates toll-like receptor 2 signaling. J. Virol. 76:8729–8736

    PubMed  CAS  Google Scholar 

  23. Kurt-Jones, E.A., Popova, L., Kwinn, L., Haynes, L.M., Jones, L.P., Tripp, R.A., Walsh, E.E., Freeman, M.W., Golenbock, D.T., Anderson, L.J. & Finberg, R.W., 2000, Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat. Immunol. 1:398–401

    PubMed  CAS  Google Scholar 

  24. Alexopoulou, L., Holt, A.C., Medzhitov, R. & Flavell, R.A., 2001, Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732–738

    PubMed  CAS  Google Scholar 

  25. Diebold, S.S., Kaisho, T., Hemmi, H., Akira, S. & Reis e Sousa, C., 2004, Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529–1531

    PubMed  CAS  Google Scholar 

  26. Heil, F., Hemmi, H., Hochrein, H., Ampenberger, F., Kirschning, C., Akira, S., Lipford, G., Wagner, H. & Bauer, S., 2004, Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303:1526–1529

    PubMed  CAS  Google Scholar 

  27. Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S. & Fujita, T., 2004, The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 5:730–7

    PubMed  CAS  Google Scholar 

  28. tenOever, B.R., Servant, M.J., Grandvaux, N., Lin, R. & Hiscott, J., 2002, Recognition of the measles virus nucleocapsid as a mechanism of IRF-3 activation. J. Virol. 76:3659–3669

    PubMed  CAS  Google Scholar 

  29. tenOever, B.R., Sharma, S., Zou, W., Sun, Q., Grandvaux, N., Julkunen, I., Hemmi, H., Yamamoto, M., Akira, S., Yeh, W.C., Lin, R. & Hiscott, J., 2004, Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity. J. Virol. 78:10636–10649

    PubMed  CAS  Google Scholar 

  30. Kim, M.J., Latham, A.G. & Krug, R.M., 2002, Human influenza viruses activate an interferon-independent transcription of cellular antiviral genes: Outcome with influenza A virus is unique. Proc. Natl. Acad. Sci. (USA) 99:10096–10101

    CAS  Google Scholar 

  31. Ludwig, S., Planz, O., Pleschka, S. & Wolff, T., 2003, Influenza-virus-induced signaling cascades: targets for antiviral therapy? Trends Mol. Med. 9:46–52

    PubMed  CAS  Google Scholar 

  32. Isaacs, A. & Lindenmann, J., 1957, Virus interference. 1. The interferon. Proc. R. Soc. Lond. B. 147:258–267

    PubMed  CAS  Google Scholar 

  33. Isaacs, A. & Burke, D.C., 1958, Mode of action of interferon. Nature 4642:1073–1076

    Google Scholar 

  34. Lindenmann, J., 1960, Interferon und inverse Interferenz. Zeitschr. f. Hygiene 146:287–309

    CAS  Google Scholar 

  35. García-Sastre, A., Egorov, A., Matassov, D., Brandt, S., Levy, D.E., Durbin, J.E., Palese, P. & Muster, T., 1998, Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252:324–330

    PubMed  Google Scholar 

  36. Enami, M. & Palese, P., 1991, High-efficiency formation of influenza virus transfectants. J. Virol. 65:2711–2713

    PubMed  CAS  Google Scholar 

  37. Diaz, M.O., Ziemin, S., Le Beau, M.M., Pitha, P., Smith, S.D., Chilcote, R.R. & Rowley, J.D., 1988, Homozygous deletion of the alpha-and beta 1-interferon genes in human leukemia and derived cell lines. Proc. Natl. Acad. Sci. USA 85:5259–5263

    PubMed  CAS  Google Scholar 

  38. Sekellick, M.J., Biggers, W.J. & Marcus, P.I., 1990, Development of the interferon system. I. In chicken cells development in ovo continues on time in vitro. In Vitro Cell. Dev. Biol. 26:997–1003

    PubMed  CAS  Google Scholar 

  39. Talon, J., Salvatore, M., O’Neill, R.E., Nakaya, Y., Zheng, H., Muster, T., García-Sastre, A. & Palese, P., 2000, Influenza A and B viruses expressing altered NS1 proteins: a vaccine approach. Proc. Natl. Acad. Sci. (USA) 97:4309–4314

    CAS  Google Scholar 

  40. Talon, J., Horvath, C.M., Polley, R., Basler, C.F., Muster, T., Palese, P. & García-Sastre, A., 2000, Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein. J. Virol. 74:7989–7996

    PubMed  CAS  Google Scholar 

  41. Wang, X., Li, M., Zheng, H., Muster, T., Palese, P., Beg, A.A. & García-Sastre, A., 2000, Influenza A virus NS1 protein prevents the activation of NF-κB and induction of type I IFN. J. Virol. 74:11566–11573

    PubMed  CAS  Google Scholar 

  42. Diebold, S.S., Montoya, M., Unger, H., Alexopoulou, L., Roy, P., Haswell, L.E., Al-Shamkhani, A., Flavell, R., Borrow, P. & Reis e Sousa, C., 2003, Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature 424:324–328

    PubMed  CAS  Google Scholar 

  43. Dauber, B., Heins, G. & Wolff, T., 2004, The influenza B virus nonstructural NS1 protein is essential for efficient viral growth and antagonizes beta interferon induction. J. Virol. 78:1865–1872

    PubMed  CAS  Google Scholar 

  44. Ludwig, S., Wang, X., Ehrhardt, C., Zheng, H., Donelan, N., Planz, O., Pleschka, S., García-Sastre, A., Heins, G. & Wolff, T., 2002, The influenza A virus NS1 protein inhibits activation of Jun N-terminal Kinase and AP-1 transcription factors. J. Virol. 76:11166–11171

    PubMed  CAS  Google Scholar 

  45. Wang, X., Basler, C.F., Williams, B.R.G., Silverman, R.H., Palese, P. & García-Sastre, A., 2002, Functional replacement of the carboxy-terminal two thirds of the influenza A virus NS1 protein with short heterologous dimerization domains. J. Virol. 76:12951–12962

    PubMed  CAS  Google Scholar 

  46. Hatada, E. & Fukuda, R., 1992, Binding of influenza A virus NS1 protein to dsRNA in vitro. J. Gen. Virol. 73:3325–3329

    PubMed  CAS  Google Scholar 

  47. Chien, C.Y., Tejero, R., Huang, Y., Zimmerman, D.E., Rios, C.B., Krug, R.M. & Montelione, G.T., 1997, A novel RNA-binding motif in influenza A virus non-structural protein 1. Nat. Struct. Biol. 4:891–895

    PubMed  CAS  Google Scholar 

  48. Kittel, C., Sereinig, S., Ferko, B., Stasakova, J., Romanova, J., Wolkerstorfer, A., Katinger, H. & Egorov, A., 2004, Rescue of influenza virus expressing GFP from the NS1 reading frame. Virology 324:67–73

    PubMed  CAS  Google Scholar 

  49. Enami, M. & Enami, K., 2000, Characterization of influenza virus NS1 protein by using a novel helper-virus-free reverse genetic system. J.Virol. 74:5556–5561

    PubMed  CAS  Google Scholar 

  50. Wang, W., Riedel, K., Lynch, P., Chien, C.Y., Montelione, G.T. & Krug, R.M., 1999, RNA binding by the novel helical domain of the influenza virus NS1 protein requires its dimer structure and a small number of specific basic amino acids. RNA 5:195–205

    PubMed  CAS  Google Scholar 

  51. Donelan, N., Basler, C.F. & García-Sastre, A., 2003, A recombinant influenza A virus expressing an RNA-binding defective NS1 protein induces high levels of IFN-ß and is attenuated in mice. J. Virol. 77:13257–13266

    PubMed  CAS  Google Scholar 

  52. Geiss, G.K., Salvatore, M., Tumpey, T.M., Carter, V.S., Wang, X., Basler, C.F., Taubenberger, J.K., Bumgarner, R.E., Palese, P., Katze, M.G. & García-Sastre, A., 2002, Cellular transcriptional profiling in influenza A virus infected lung epithelial cells: the role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza. Proc. Natl. Acad. Sci. (USA) 99:10736–10741

    CAS  Google Scholar 

  53. Wolff, T., O’Neill, R.E. & Palese, P., 1996, Interaction cloning of NS1-I, a human protein that binds to the nonstructural NS1 proteins of influenza A and B viruses. J. Virol. 70:5363–5372

    PubMed  CAS  Google Scholar 

  54. Wolff, T., O’Neill, R.E. & Palese, P., 1998, NS1-binding protein (NS1-BP): A novel human protein that interacts with the influenza A virus nonstructural NS1 protein is relocalized in the nucleus of infected cells. J. Virol. 72:7170–7180

    PubMed  CAS  Google Scholar 

  55. Nemeroff, M.E., Barabino, S.M., Li, Y., Keller, W. & Krug, R.M., 1998, Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3’end formation of cellular pre-mRNAs. Mol. Cell 1:991–1000

    PubMed  CAS  Google Scholar 

  56. Falcon, A.M., Fortes, P., Marion, R.M., Beloso, A. & Ortín, J., 1999, Interaction of influenza virus NS1 protein and the human homologue of Staufen in vivo and in vitro. Nucleic Acids Res. 27:2241–2247

    PubMed  CAS  Google Scholar 

  57. Chen, Z., Li, Y. & Krug, R.M., 1999, Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3′-end processing machinery. EMBO J. 18:2273–2283

    PubMed  CAS  Google Scholar 

  58. Aragón, T., de La Luna, S., Novoa, I., Carrasco, L., Ortín, J. & Nieto, A., 2000, Eukaryotic translation initiation factor 4GI is a cellular target for NS1 protein, a translational activator of influenza virus. Mol. Cell. Biol. 20:6259–6268

    PubMed  Google Scholar 

  59. Burgui, I., Aragon, T., Ortin, J. & Nieto, A., 2003, PABP1 and eIF4GI associate with influenza virus NS1 protein in viral mRNA translation initiation complexes. J. Gen. Virol. 84:3263–3274

    PubMed  CAS  Google Scholar 

  60. Qiu, Y., Nemeroff, M. & Krug, R.M., 1995, The influenza virus NS1 protein binds to a specific region in human U6 snRNA and inhibits U6-U2 and U6-U4 snRNA interactions during splicing. RNA 1:304–316

    PubMed  CAS  Google Scholar 

  61. Li, Y., Chen, Z.Y., Wang, W., Baker, C.C. & Krug, R.M., 2001, The 3′-end-processing factor CPSF is required for the splicing of single-intron pre-mRNAs in vivo. RNA 7:920–931

    PubMed  CAS  Google Scholar 

  62. Fortes, P., Beloso, A. & Ortín, J., 1994, Influenza virus NS1 protein inhibits pre-mRNA splicing and blocks mRNA nucleocytoplasmic transport. EMBO J. 13:704–712

    PubMed  CAS  Google Scholar 

  63. Lu, Y., Qian, X.Y. & Krug, R.M., 1994, The influenza virus NS1 protein: a novel inhibitor of pre-mRNA splicing. Genes Dev. 8:1817–1828

    PubMed  CAS  Google Scholar 

  64. Marión, R.M., Aragón, T., Beloso, A., Nieto, A. & Ortín, J., 1997, The N-terminal half of the influenza virus NS1 protein is sufficient for nuclear retention of mRNA and enhancement of viral mRNA translation. Nucleic Acids Res. 25:4271–4277

    PubMed  Google Scholar 

  65. Shimizu, K., Iguchi, A., Gomyou, R. & Ono, Y., 1999, Influenza virus inhibits cleavage of the HSP70 pre-mRNAs at the polyadenylation site. Virology 254:213–219

    PubMed  CAS  Google Scholar 

  66. Noah, D.L., Twu, K.Y. & Krug, R.M., 2003, Cellular antiviral responses against influenza A virus are countered at the posttranscriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3′ end processing of cellular premRNAS. Virology 307:386–395

    PubMed  CAS  Google Scholar 

  67. Williams, B.R., 1999, PKR; a sentinel kinase for cellular stress. Oncogene 18:6112–6120

    PubMed  CAS  Google Scholar 

  68. Gale, M.J. & Katze, M.G., 1998, Molecular mechanisms of interferon resistance mediated by viral-directed inhibition of PKR, the interferon-induced protein kinase. Pharmacol. Ther. 78:29–46

    PubMed  CAS  Google Scholar 

  69. Lu, Y., Wambach, M., Katze, M.G. & Krug, R.M., 1995, Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor. Virology 214:222–228

    PubMed  CAS  Google Scholar 

  70. Tan, S.L. & Katze, M.G., 1998, Biochemical and genetic evidence for complex formation between the influenza A virus NS1 protein and the interferon-induced PKR protein kinase. J. Interferon Cytokine Res. 18:757–766

    PubMed  CAS  Google Scholar 

  71. Hatada, E., Saito, S. & Fukuda, R., 1999, Mutant influenza viruses with a defective NS1 protein cannot block the activation of PKR in infected cells. J. Virol. 73:2425–2433

    PubMed  CAS  Google Scholar 

  72. Salvatore, M., Basler, C.F., Parisien, J.-P., Horvath, C.M., Bourmakina, S., Zheng, H., Muster, T., Palese, P. & García-Sastre, A., 2002, Effects of influenza A virus NS1 protein on protein expression: the NS1 protein enhances translation and is not required for shutoff of host protein synthesis. J. Virol. 76:1206–1212

    PubMed  CAS  Google Scholar 

  73. Bergmann, M., García-Sastre, A., Carnero, E., Pehamberger, H., Wolff, K., Palese, P. & Muster, T., 2000, Influenza virus NS1 protein counteracts PKR-mediated inhibition of replication. J. Virol. 74:6203–6206

    PubMed  CAS  Google Scholar 

  74. Dubrovina, T.I., Egorov, A.I., Ivanova, I.A., Pokhil’ko, A.V. & Poliak, R.I., 1995, The effect of mutation in the NS gene on the biological properties of the influenza virus. Zh. Mikrobiol. Epidemiol. Immunobiol. 3:75–79

    PubMed  Google Scholar 

  75. Sekellick, M.J., Carra, S.A., Bowman, A., Hopkins, D.A. & Marcus, P.I., 2000, Transient resistance of influenza virus to interferon action attributed to random multiple packaging and activity of NS genes. J. Interferon Cytokine Res. 20:963–970

    PubMed  CAS  Google Scholar 

  76. Seo, S.H., Hoffmann, E. & Webster, R.G., 2002, Lethal H5N1 influenza viruses escape host antiviral cytokine responses. Nat. Med. 8:950–954

    PubMed  CAS  Google Scholar 

  77. Chang, H.W., Watson, J.C. & Jacobs, B.L., 1992, The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase. Proc. Natl. Acad. Sci. USA 89:4825–4829

    PubMed  CAS  Google Scholar 

  78. Smith, E.J., Marié, I., Prakash, A., García-Sastre, A. & Levy, D.E., 2001, IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or IκB kinase but is blocked by vaccinia virus E3L protein. J. Biol. Chem. 276:8951–8957

    PubMed  CAS  Google Scholar 

  79. Xiang, Y., Condit, R.C., Vijaysri, S., Jacobs, B., Williams, B.R. & Silverman, R.H., 2002, Blockade of interferon induction and action by the E3L double-stranded RNA binding proteins of vaccinia virus. J. Virol. 76:5251–5259

    PubMed  CAS  Google Scholar 

  80. Basler, C.F., Wang, X., Mühlberger, E., Volchkov, V., Paragas, J., Klenk, H.-D., García-Sastre, A. & Palese, P., 2000, The Ebola virus VP35 protein functions as a type I interferon antagonist. Proc. Natl. Acad. Sci. (USA) 97:12289–12294

    CAS  Google Scholar 

  81. Basler, C.F., Mikulasova, A., Martinez-Sobrido, L., Paragas, J., Muhlberger, E., Bray, M., Klenk, H.D., Palese, P. & García-Sastre, A., 2003, The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J. Virol. 77:7945–7956

    PubMed  CAS  Google Scholar 

  82. He, B., Gross, M. & Roizman, B., 1997, The γ(1) 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc. Natl. Acad. Sci. (USA) 94:843–848

    CAS  Google Scholar 

  83. Jing, X., Cerveny, M., Yang, K. & He, B., 2004, Replication of herpes simplex virus 1 depends on the γ134.5 functions that facilitate virus response to interferon and egress in the different stages of productive infection. J. Virol. 78:7653–7666

    PubMed  CAS  Google Scholar 

  84. Park, M.S., García-Sastre, A., Cros, J.F., Basler, C.F. & Palese, P., 2003, Newcastle disease virus V protein is a determinant of host range restriction. J. Virol. 77:9522–9532

    PubMed  CAS  Google Scholar 

  85. Didcock, L., Young, D.F., Goodbourn, S. & Randall, R.E., 1999, The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation. J.Virol. 73:9928–9933

    PubMed  CAS  Google Scholar 

  86. Poole, E., He, B., Lamb, R.A., Randall, R.E. & Goodbourn, S., 2002, The V proteins of simian virus 5 and other paramyxoviruses inhibit induction of interferon-beta. Virology 303:33–46

    PubMed  CAS  Google Scholar 

  87. Katze, M.G., DeCorato, D. & Krug, R.M., 1986, Cellular mRNA translation is blocked at both initiation and elongation after infection by influenza virus or adenovirus. J. Virol. 60:1027–1039

    PubMed  CAS  Google Scholar 

  88. Feigenblum, D. & Schneider, R.J., 1993, Modification of eukaryotic initiation factor 4F during infection by influenza virus. J. Virol. 67:3027–3035

    PubMed  CAS  Google Scholar 

  89. Zürcher, T., Marión, R.M. & Ortín, J., 2000, Protein synthesis shut-off induced by influenza virus infection is independent of PKR activity. J.Virol. 74:8781–8784

    PubMed  Google Scholar 

  90. Lee, T.G., Tomita, J., Hovanessian, A.G. & Katze, M.G., 1990, Purification and partial characterization of a cellular inhibitor of the interferon-induced protein kinase of Mr 68,000 from influenza virus-infected cells. Proc. Natl. Acad. Sci. (USA) 87:6208–6212

    CAS  Google Scholar 

  91. Lee, T.G., Tomita, J., Hovanessian, A.G. & Katze, M.G., 1992, Characterization and regulation of the 58,000-dalton cellular inhibitor of the interferon-induced, dsRNA-activated protein kinase. J. Biol. Chem. 267:14238–14243

    PubMed  CAS  Google Scholar 

  92. Levy, D.E. & García-Sastre, A., 2001, The virus battles: IFN induction of the antiviral state and mechanisms of viral evasion. Cytokine Growth Factor Rev. 12:143–156.

    PubMed  CAS  Google Scholar 

  93. Donelan, N.R., Dauber, B., Wang, X., Basler, C.F., Wolff, T. & García-Sastre, A., 2004, The N-and C-terminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3 and IFN? promoter activation. J. Virol.: in press

    Google Scholar 

  94. Wang, W. & Krug, R.M., 1996, The RNA-binding and effector domains of the viral NS1 protein are conserved to different extents among influenza A and B viruses. Virology 223:41–50

    PubMed  CAS  Google Scholar 

  95. Yuan, W., Aramini, J.M., Montelione, G.T. & Krug, R.M., 2002, Structural basis for ubiquitin-like ISG 15 protein binding to the NS1 protein of influenza B virus: A protein-protein interaction function that is not shared by the corresponding N-terminal domain of the NS1 protein of influenza A virus. Virology 304:291–301

    PubMed  CAS  Google Scholar 

  96. Yuan, W. & Krug, R.M., 2001, Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. EMBO J. 20:362–371

    PubMed  CAS  Google Scholar 

  97. Zhao, C., Beaudenon, S.L., Kelley, M.L., Waddell, M.B., Yuan, W., Schulman, B.A., Huibregtse, J.M. & Krug, R.M., 2004, The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-alpha/beta-induced ubiquitin-like protein. Proc. Natl. Acad. Sci. (USA) 101:7578–7582

    CAS  Google Scholar 

  98. Malakhova, O.A., Yan, M., Malakhov, M.P., Yuan, Y., Ritchie, K.J., Kim, K.I., Peterson, L.F., Shuai, K. & Zhang, D.E., 2003, Protein ISGylation modulates the JAK-STAT signaling pathway. Genes Dev. 17:455–460

    PubMed  CAS  Google Scholar 

  99. Hagmaier, K., Jennings, S., Buse, J., Weber, F. & Kochs, G., 2003, Novel gene product of thogoto virus segment 6 codes for an interferon antagonist. J. Virol. 77:2747–2752

    PubMed  CAS  Google Scholar 

  100. Kochs, G., Weber, F., Gruber, S., Delvendahl, A., Leitz, C. & Haller, O., 2000, Thogoto virus matrix protein is encoded by a spliced mRNA. J. Virol. 74:10785–10789

    PubMed  CAS  Google Scholar 

  101. Pichlmair, A., Buse, J., Jennings, S., Haller, O., Kochs, G. & Staeheli, P., 2004, Thogoto Virus Lacking Interferon antagonistic Protein ML Is Strongly Attenuated in Newborn Mx1-Positive but Not Mx1-Negative Mice. J. Virol. 78:11422–11424

    PubMed  CAS  Google Scholar 

  102. Jennings, S., Martínez-Sobrido, L., García-Sastre, A., Weber, F. & Kochs, G., Thogoto virus ML protein suppresses IRF3 function. submitted

    Google Scholar 

  103. Enami, K., Sato, T.A., Nakada, S. & Enami, M., 1994, Influenza virus NS1 protein stimulates translation of the M1 protein. J. Virol. 68:1432–1437

    PubMed  CAS  Google Scholar 

  104. de la Luna, S., Fortes, P., Beloso, A. & Ortín, J., 1995, Influenza virus NS1 protein enhances the rate of translation initiation of viral mRNAs. J. Virol. 69:2427–2433

    PubMed  Google Scholar 

  105. Falcon, A.M., Marion, R.M., Zurcher, T., Gomez, P., Portela, A., Nieto, A. & Ortin, J., 2004, Defective RNA replication and late gene expression in temperature-sensitive influenza viruses expressing deleted forms of the NS1 protein. J. Virol. 78:3880–3888

    PubMed  CAS  Google Scholar 

  106. Schultz-Cherry, S., Dybdahl-Sissoko, N., Neumann, G., Kawaoka, Y. & Hinshaw, V.S., 2001, Influenza virus NS1 protein induces apoptosis in cultured cells. J. Virol. 75:7875–7881

    PubMed  CAS  Google Scholar 

  107. Morris, S.J., Smith, H. & Sweet, C., 2002, Exploitation of the Herpes simplex virus translocating protein VP22 to carry influenza virus proteins into cells for studies of apoptosis: direct confirmation that neuraminidase induces apoptosis and indications that other proteins may have a role. Arch. Virol. 147:961–979

    PubMed  CAS  Google Scholar 

  108. Zhirnov, O.P., Konakova, T.E., Wolff, T. & Klenk, H.D., 2002, NS1 protein of influenza A virus down-regulates apoptosis. J. Virol. 76:1617–1625

    PubMed  CAS  Google Scholar 

  109. Li, W.X., Li, H., Lu, R., Li, F., Dus, M., Atkinson, P., Brydon, E.W., Johnson, K.L., García-Sastre, A., Ball, L.A., Palese, P. & Ding, S.W., 2004, Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing. Proc. Natl. Acad. Sci. (USA) 101:1350–13555

    CAS  Google Scholar 

  110. Bucher, E., Hemmes, H., de Haan, P., Goldbach, R. & Prins, M., 2004, The influenza A virus NS1 protein binds small interfering RNAs and suppresses RNA silencing in plants. J. Gen. Virol. 85:983–991

    PubMed  CAS  Google Scholar 

  111. Delgadillo, M.O., Saenz, P., Salvador, B., Garcia, J.A. & Simon-Mateo, C., 2004, Human influenza virus NS1 protein enhances viral pathogenicity and acts as an RNA silencing suppressor in plants. J. Gen. Virol. 85:993–999

    PubMed  CAS  Google Scholar 

  112. Basler, C.F., Reid, A.H., Dybing, J.K., Janczewski, T.A., Fanning, T.G., Zheng, H., Salvatore, M., Perdue, M.L., Swayne, D.E., García-Sastre, A., Palese, P. & Taubenberger, J.K., 2001, Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes. Proc. Natl. Acad. Sci. (USA) 98:2746–2751

    CAS  Google Scholar 

  113. Seo, S.H., Hoffmann, E. & Webster, R.G., 2004, The NS1 gene of H5N1 influenza viruses circumvents the host antiviral cytokine responses. Virus Res. 103:107–113

    PubMed  CAS  Google Scholar 

  114. Cheung, C.Y., Poon, L.L., Lau, A.S., Luk, W., Lau, Y.L., Shortridge, K.F., Gordon, S., Guan, Y. & Peiris, J.S., 2002, Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? Lancet 360:1831–1837

    PubMed  CAS  Google Scholar 

  115. Ferko, B., Stasakova, J., Sereinig, S., Romanova, J., Katinger, D., Niebler, B., Katinger, H. & Egorov, A., 2001, Hyperattenuated recombinant influenza A virus nonstructural-protein-encoding vectors induce human immunodeficiency virus type 1 Nef-specific systemic and mucosal immune responses in mice. J Virol 75:8899–908

    PubMed  CAS  Google Scholar 

  116. Takasuka, N., Enami, M., Itamura, S. & Takemori, T., 2002, Intranasal inoculation of a recombinant influenza virus containing exogenous nucleotides in the NS segment induces mucosal immune response against the exogenous gene product in mice. Vaccine 20:1579–1585

    PubMed  CAS  Google Scholar 

  117. Efferson, C.L., Schickli, J., Ko, B.K., Kawano, K., Mouzi, S., Palese, P., García-Sastre, A. & Ioannides, C.G., 2003, Activation of tumor antigen-specific cytotoxic T lymphocytes (CTLs) by human dendritic cells infected with an attenuated influenza A virus expressing a CTL epitope derived from the HER-2/neu proto-oncogene. J Virol 77:7411–7424

    PubMed  CAS  Google Scholar 

  118. Bergmann, M., Romirer, I., Sachet, M., Fleischhacker, R., García-Sastre, A., Palese, P., Wolff, K., Pehamberger, H., Jakesz, R. & Muster, T., 2001, A genetically engineered influenza A virus with ras-dependent oncolytic properties. Cancer Res. 61:8188–8193

    PubMed  CAS  Google Scholar 

  119. Muster, T., Rajtarova, J., Sachet, M., Unger, H., Fleischhacker, R., Romirer, I., Grassauer, A., Url, A., García-Sastre, A., Wolff, K., Pehamberger, H. & Bergmann, M., 2004, Interferon resistance promotes oncolysis by influenza virus NS1-deletion mutants. Int. J. Cancer 110:15–21

    PubMed  CAS  Google Scholar 

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  1. Department of Microbiology, Mount Sinai School of Medicine, New York, NY, USA

    Adolfo García-Sastre

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  1. Mount Sinai School of Medicine, New York, NY, USA

    Peter Palese

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García-Sastre, A. (2005). Interferon Antagonists of Influenza Viruses. In: Palese, P. (eds) Modulation of Host Gene Expression and Innate Immunity by Viruses. Springer, Dordrecht. https://doi.org/10.1007/1-4020-3242-0_5

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