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virus RNAs EBER-1 and EBER-2 and adenovirus VAI RNA. Nucleic Acids Res. 1993, 21, 4483 4490. 46. Lu, Y.; Qian, X. Y.; Krug, R. M. The in uenza virus NS1 protein: a novel inhibitor of premRNA splicing. Genes Dev. 1994, 8, 1817 1828. 47. Li, W.-X.; Li, H.; Lu, R.; Li, F.; Dus, M.; et al. Interferon antagonist proteins of in uenza and vaccinia viruses are suppressors of RNA silencing. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 1350 1355. 48. Hatada, E.; Saito, S.; Fukuda, R. Mutant in uenza viruses with a defective NS1 protein cannot block the activation of PKR in infected cells. Virology 1999, 73, 2425 2433. 49. Fortes, P.; Beloso, A.; Ortin, J. In uenza virus NS1 protein inhibits pre-mRNA splicing and blocks mRNA nucleocytoplasmic transport. EMBO J. 1994, 13, 704 712. 50. Gale, M. J.; Korth, M. J.; Tang, N.; Tan, S. L.; Hopkins, D. A.; et al. Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Virology 1997, 230, 217 227. 51. Taylor, D. R.; Shi, S. T.; Romano, P. R.; Barber, G. N.; Lai, M. M. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 1999, 285, 107 110. 52. Dever, T. E.; Sripriya, R.; McLachlin, J. R.; Lu, J.; Fabian-Matcher, J. R.; et al. Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2-a kinase homolog. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 4164 4169. 53. McMillan, N. A.; Chun, R. F.; Siderovski, D. P.; Galabru, J.; Toone, W. M.; et al. HIV-1 Tat directly interacts with the interferon-induced, double-stranded-RNA-dependent kinase PKR. Virology 1995, 213, 413 424. 54. Brand, S. R.; Kobayashi, R.; Mathews, M. B. The Tat protein of human immunode ciency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR. J. Biol. Chem. 1997, 272, 8388 8395. 55. He, B.; Gross, M.; Roizman, B. The gamma1 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1a to dephosphorylate the alpha 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. U.S.A. 1997, 94, 843 848. 56. Cayley, P. J.; Davies, J. A.; McCullagh, K. G.; Kerr, I. M. Activation of the ppp(A20 p)nA system in interferon-treated, herpes simplex virus-infected cells and evidence for novel inhibitors of the ppp(A20 p)nA-dependent RNase. Eur. J. Biochem. 1984, 15, 165 174. 57. Cayley, P. J.; Knight, M.; Kerr, I. M. Virus-mediated inhibition of the ppp(A20 p)nA system and its prevention by interferon. Biochem. Biophys. Res. Commun. 1982, 104, 376 382. 58. Black, T. L.; Barber, G. N.; Katze, M. G. Degradation of the interferon-induced 68,000Mr protein kinase by poliovirus requires RNA. J. Virol. 1993, 67, 791 800. 59. Black, T. L.; Safer, B.; Hovanessian, A. G.; Katze, M. G. The cellular 68,000Mr protein kinase is highly autophosphorylated and activated yet signi cantly degraded during poliovirus infection: implications for translational regulation. J. Virol. 1989, 63, 2244 2251. 60. Sharp, T. V.; Moonan, F.; Romashko, A.; Joshi, B.; Barber, G. N.; et al. The vaccinia virus E3L gene product interacts with both the regulatory and the substrate binding regions of PKR: implications for PKR autoregulation. Virology 1998, 250, 302 315. 61. Romano, P. R.; Zhang, F.; Tan, S.-L.; Garcia-Barrio, M. T.; Katze, M. G.; et al. Inhibition of double-stranded RNA-dependent protein kinase PKR by vaccinia virus E3:
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role of complex formation and the E3 N-terminal domain. Mol. Cell. Biol. 1998, 18, 7304 7316. 62. Rivas, C.; Gil, J.; Melkova, Z.; Esteban, M.; Diaz-Guerra, M. Vaccinia virus E3L protein is an inhibitor of the interferon (IFN)-induced 2-5A synthetase enzyme. Virology 1998, 243, 406 414. 63. Lee, T. G.; Tomita, J.; Hovanessian, A. G.; Katze, M. G. Characterization and regulation of the 58,000-dalton cellular inhibitor of the interferon-induced, dsRNA-activated protein kinase. J. Biol. Chem. 1992, 267, 14238 14243. 64. Lee, T. G.; Tomita, J.; Hovanessian, A. G.; Katze, M. G. Puri cation and partial characterization of a cellular inhibitor of the interferon-induced protein kinase of Mr 68,000 from in uenza virus-infected cells. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 6208 6212. 65. Lee, T. G.; Tang, N.; Thompson, S.; Miller, J.; Katze, M. G. The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat family of proteins. Mol. Cell. Biol. 1994, 14, 2331 2342. 66. Haig, D. M. Subversion and piracy: DNA viruses and immune evasion. Res. Vet. Sci. 2001, 70, 205 219. 67. Haig, D. M.; Thomson, J.; McInnes, C.; McCaughan, C.; Imlach, W.; et al. Orf virus immuno-modulation and the host immune response. Vet. Immunol. Immunopathol. 2002, 87, 395 399. 68. Melville, M. W.; Hansen, W. J.; Freeman, B. C.; Welch, W. J.; Katze, M. G. The molecular chaperone hsp40 regulates the activity of P58IPK, the cellular inhibitor of PKR. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 97 102. 69. Rice, A. P.; Roberts, W. K.; Kerr, I. M. 2-5A accumulates to high levels in interferontreated, vaccinia virus-infected cells in the absence of any inhibition of virus replication. J. Virol. 1984, 50(1), 220 228. 70. Paez, E.; Esteban, M. Nature and mode of action of vaccinia virus products that block activation of the interferon-mediated ppp(A20 p)nA-synthetase. Virology 1984, 134(1), 29 39. 71. Hersh, C. L.; Brown, R. E.; Roberts, W. K.; Swyryd, E. A.; Kerr, I. M.; Stark, G. R. Simian virus 40-infected, interferon-treated cells contain 20 ,50 -oligoadenylates which do not activate cleavage of RNA. J. Biol. Chem. 1984, 259(3), 1731 1737. 72. Laurence, L.; Roux, D.; Cailla, H.; Riviere, Y.; Marcovistz, R.; Hovanessian, A. Comparison of the effects of rabies virus infection and of combined interferon and poly(I) poly(C) treatment on the levels of 20 ,50 -adenyladenosine oligonucleotides in different organs of mice. Virology 1985, 143(1), 290 299. 73. Marcovistz, R.; Germano, P. M.; Riviere,Y.; Tsiang, H.; Hovanessian, A. G. The effect of interferon treatment in rabies prophylaxis in immunocompetent, immunosuppressed, and immunode cient mice. J. Interferon Res. 1987, 7(1), 17 27. 74. Witt, P. L.; Marie, I.; Robert, N.; Irizarry, A.; Borden, E. C.; Hovanessian, A. G. Isoforms p69 and p100 of 20 ,50 -oligoadenylate synthetase induced differentially by interferons in vivo and in vitro. J. Interferon Res. 1993, 13, 17 23. 75. Schroder, H. C.; Wenger, R.; Kuchino, Y.; Muller, W. E. G. Modulation of nuclear matrixassociated 20 ,50 -oligoadenylate metabolism and ribonuclease L activity in H9 cells by human immunode ciency virus. J. Biol. Chem. 1989, 264, 5669 5673.
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