Activation of the antiviral kinase PKR and viral countermeasures

Viruses

Volumn 1, Issue 3, 2009, Pages 523-544

  Dauber, Bianca ^a   Wolff, Thorsten ^b  

^a UNIVERSITY OF ALBERTA   (Canada)

^b ROBERT KOCH INSTITUTE   (Germany)

Author keywords

dsRNA; Immune evasion; Innate immunity; PKR; Virus

Indexed keywords

EID: 77954947916     PISSN: 19994915     EISSN: None     Source Type: Journal    
DOI: 10.3390/v1030523     Document Type: Review

References (152)

1. Garcia-Sastre, A.; Biron, C.A. Type 1 interferons and the virus-host relationship: A lesson in detente. Science 2006, 312, 879-882.
2. Sadler, A.J.; Williams, B.R. Interferon-inducible antiviral effectors. Nat. Rev. Immunol. 2008, 8, 559-568.
3. Haines, G.K., 3rd; Panos, R.J.; Bak, P.M.; Brown, T.; Zielinski, M.; Leyland, J.; Radosevich, J.A. Interferon-responsive protein kinase (p68) and proliferating cell nuclear antigen are inversely distributed in head and neck squamous cell carcinoma. Tumor Biol. 1998, 19, 52-59.
4. Kuhen, K.L.; Samuel, C.E. Mechanism of interferon action: Functional characterization of positive and negative regulatory domains that modulate transcriptional activation of the human RNA-dependent protein kinase Pkr promoter. Virology 1999, 254, 182-195.
5. Meurs, E.; Chong, K.; Galabru, J.; Thomas, N.S.; Kerr, I.M.; Williams, B.R.; Hovanessian, A.G. Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Cell 1990, 62, 379-390.
6. Cole, J.L. Activation of PKR: An open and shut case? Trends Biochem. Sci 2007, 32, 57-62.
7. Galabru, J.; Hovanessian, A. Autophosphorylation of the protein kinase dependent on doublestranded RNA. J. Biol. Chem. 1987, 262, 15538-15544.
8. Romano, P.R.; Zhang, F.; Tan, S.L.; Garcia-Barrio, M.T.; Katze, M.G.; Dever, T.E.; Hinnebusch, A.G. Inhibition of double-stranded RNA-dependent protein kinase PKR by vaccinia virus E3: Role of complex formation and the E3 N-terminal domain. Mol. Cell. Biol. 1998, 18, 7304-7316.
9. Dey, M.; Cao, C.; Dar, A.C.; Tamura, T.; Ozato, K.; Sicheri, F.; Dever, T.E. Mechanistic link between PKR dimerization, autophosphorylation, and eIF2alpha substrate recognition. Cell 2005, 122, 901-913.
10. Dar, A.C.; Dever, T.E.; Sicheri, F. Higher-order substrate recognition of eIF2alpha by the RNAdependent protein kinase PKR. Cell 2005, 122, 887-900.
11. Pathak, V.K.; Schindler, D.; Hershey, J.W. Generation of a mutant form of protein synthesis initiation factor eIF-2 lacking the site of phosphorylation by eIF-2 kinases. Mol. Cell. Biol. 1988, 8, 993-995.
12. Samuel, C.E. The eIF-2 alpha protein kinases, regulators of translation in eukaryotes from yeasts to humans. J. Biol. Chem. 1993, 268, 7603-7606.
13. Hershey, J.W. Translational control in mammalian cells. Annu. Rev. Biochem 1991, 60, 717-755.
14. Garcia, M.A.; Gil, J.; Ventoso, I.; Guerra, S.; Domingo, E.; Rivas, C.; Esteban, M. Impact of protein kinase PKR in cell biology: From antiviral to antiproliferative action. Microbiol. Mol. Biol. Rev. 2006, 70, 1032-1060.
15. Hovanessian, A.G.; Galabru, J. The double-stranded RNA-dependent protein kinase is also activated by heparin. Eur. J. Biochem. 1987, 167, 467-473.
16. Patel, R.C.; Sen, G.C. PACT, a protein activator of the interferon-induced protein kinase, PKR. EMBO J. 1998, 17, 4379-4390.
17. Daher, A.; Laraki, G.; Singh, M.; Melendez-Pena, C.E.; Bannwarth, S.; Peters, A.H.; Meurs, E.F.; Braun, R.E.; Patel, R.C.; Gatignol, A. TRBP control of PACT-induced phosphorylation of protein kinase R is reversed by stress. Mol. Cell. Biol. 2009, 29, 254-265.
18. Hovanessian, A.G. On the discovery of interferon-inducible, double-stranded RNA activated enzymes: The 2'-5'oligoadenylate synthetases and the protein kinase PKR. Cytokine Growth Factor Rev. 2007, 18, 351-361.
19. Kawai, T.; Akira, S. Toll-like receptor and RIG-I-like receptor signaling. Ann. N.Y. Acad. Sci. 2008, 1143, 1-20.
20. Yoneyama, M.; Fujita, T. Structural mechanism of RNA recognition by the RIG-I-like receptors. Immunity 2008, 29, 178-181.
21. Schlee, M.; Hartmann, E.; Coch, C.; Wimmenauer, V.; Janke, M.; Barchet, W.; Hartmann, G. Approaching the RNA ligand for RIG-I? Immunol. Rev. 2009, 227, 66-74.
22. Hovanessian, A.G.; Kerr, I.M. The (2'-5') oligoadenylate (pppA2'-5'A2'-5'A) synthetase and protein kinase(s) from interferon-treated cells. Eur. J. Biochem. 1979, 93, 515-526.
23. Manche, L.; Green, S.R.; Schmedt, C.; Mathews, M.B. Interactions between double-stranded RNA regulators and the protein kinase DAI. Mol. Cell. Biol. 1992, 12, 5238-5248.
24. Michelson, A.M.; Massoulie, J.; Guschlbauer, W. Synthetic polynucleotides. Progr. Nucl. Acid. Res. Mol. Biol. 1967, 6, 83-141.
25. Schlee, M.; Barchet, W.; Hornung, V.; Hartmann, G. Beyond double-stranded RNA-type I IFN induction by 3pRNA and other viral nucleic acids. Curr. Top. Microbiol. Immunol. 2007, 316, 207-230.
26. Nallagatla, S.R.; Hwang, J.; Toroney, R.; Zheng, X.; Cameron, C.E.; Bevilacqua, P.C. 5'-triphosphate-dependent activation of PKR by RNAs with short stem-loops. Science 2007, 318, 1455-1458.
27. Nallagatla, S.R.; Bevilacqua, P.C. Nucleoside modifications modulate activation of the protein kinase PKR in an RNA structure-specific manner. Rna 2008, 14, 1201-1213.
28. Pichlmair, A.; Schulz, O.; Tan, C.P.; Naslund, T.I.; Liljestrom, P.; Weber, F.; Reis e Sousa, C. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates. 2006, 314, 997-1001.
29. Hornung, V.; Ellegast, J.; Kim, S.; Brzozka, K.; Jung, A.; Kato, H.; Poeck, H.; Akira, S.; Conzelmann, K.K.; Schlee, M.; Endres, S.; Hartmann, G. 5'-Triphosphate RNA is the ligand for RIG-I. Science 2006, 314, 994-997.
30. Myong, S.; Cui, S.; Cornish, P.V.; Kirchhofer, A.; Gack, M.U.; Jung, J.U.; Hopfner, K.P.; Ha, T. Cytosolic viral sensor RIG-I is a 5'-triphosphate-dependent translocase on double-stranded RNA. Science 2009, 323, 1070-1074.
31. Schlee, M.; Roth, A.; Hornung, V.; Hagmann, C.A.; Wimmenauer, V.; Barchet, W.; Coch, C.; Janke, M.; Mihailovic, A.; Wardle, G.; Juranek, S.; Kato, H.; Kawai, T.; Poeck, H.; Fitzgerald, K.A.; Takeuchi, O.; Akira, S.; Tuschl, T.; Latz, E.; Ludwig, J.; Hartmann, G. Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus. Immunity 2009, 31, 25-34.
32. Schmidt, A.; Schwerd, T.; Hamm, W.; Hellmuth, J. C.; Cui, S.; Wenzel, M.; Hoffmann, F.S.; Michallet, M.C.; Besch, R.; Hopfner, K.P.; Endres, S.; Rothenfusser, S. 5'-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I. Proc. Natl. Acad. Sci. USA 2009, 106, 12067-12072.
33. Cazenave, C.; Uhlenbeck, O.C. RNA template-directed RNA synthesis by T7 RNA polymerase. Proc. Natl. Acad. Sci. USA 1994, 91, 6972-6976.
34. Nacheva, G.A.; Berzal-Herranz, A. Preventing nondesired RNA-primed RNA extension catalyzed by T7 RNA polymerase. Eur. J. Biochem. 2003, 270, 1458-1465.
35. Schonborn, J.; Oberstrass, J.; Breyel, E.; Tittgen, J.; Schumacher, J.; Lukacs, N. Monoclonal antibodies to double-stranded RNA as probes of RNA structure in crude nucleic acid extracts. Nucleic Acids Res. 1991, 19, 2993-3000.
36. Colby, C.; Jurale, C.; Kates, J.R. Mechanism of synthesis of vaccinia virus double-stranded ribonucleic acid in vivo and in vitro. J. Virol. 1971, 7, 71-76.
37. Jacquemont, B.; Roizman, B. RNA synthesis in cells infected with herpes simplex virus. X. Properties of viral symmetric transcripts and of double-stranded RNA prepared from them. J. Virol. 1975, 15, 707-713.
38. Pettersson, U.; Philipson, L. Synthesis of complementary RNA sequences during productive adenovirus infection. Proc. Natl. Acad. Sci. USA 1974, 71, 4887-4891.
39. Weber, F.; Wagner, V.; Rasmussen, S.B.; Hartmann, R.; Paludan, S.R. Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. J. Virol. 2006, 80, 5059-5064.
40. Budt, M.; Niederstadt, L.; Valchanova, R.S.; Jonjic, S.; Brune, W. Specific inhibition of the PKR-mediated antiviral response by the murine cytomegalovirus proteins m142 and m143. J. Virol. 2009, 83, 1260-1270.
41. Marshall, E.E.; Bierle, C.J.; Brune, W.; Geballe, A.P. Essential role for either TRS1 or IRS1 in human cytomegalovirus replication. J. Virol. 2009, 83, 4112-4120.
42. Silverstein, S.C.; Schur, P.H. Immunofluorescent localization of double-stranded RNA in reovirus-infected cells. Virology 1970, 41, 564-566.
43. Lee, J.Y.; Marshall, J.A.; Bowden, D.S. Characterization of rubella virus replication complexes using antibodies to double-stranded RNA. Virology 1994, 200, 307-312.
44. Stollar, B.D.; Stollar, V. Immunofluorescent demonstration of double-stranded RNA in the cytoplasm of Sindbis virus-infected cells. Virology 1970, 42, 276-280.
45. Gavrilovskaya, I.N.; Lavrova, I.K.; Voroshilova, M.K.; Chumakov, M.P.; Poverenny, A.M.; Podgorodnichenko, V.K. Immunofluorescent demonstration of double-stranded RNA and virus antigen in RNA virus-infected cells. Virology 1974, 62, 276-279.
46. Miller, S.; Kastner, S.; Krijnse-Locker, J.; Buhler, S.; Bartenschlager, R. The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. J. Biol. Chem. 2007, 282, 8873-8882.
47. Targett-Adams, P.; Boulant, S.; McLauchlan, J. Visualization of double-stranded RNA in cells supporting hepatitis C virus RNA replication. J. Virol. 2008, 82, 2182-2195.
48. Westaway, E.G.; Mackenzie, J.M.; Kenney, M.T.; Jones, M.K.; Khromykh, A.A. Ultrastructure of Kunjin virus-infected cells: Colocalization of NS1 and NS3 with double-stranded RNA, and of NS2B with NS3, in virus-induced membrane structures. J. Virol. 1997, 71, 6650-6661.
49. Jacobs, B.L.; Langland, J.O. When two strands are better than one: The mediators and modulators of the cellular responses to double-stranded RNA. Virology 1996, 219, 339-349.
50. Vyas, J.; Elia, A.; Clemens, M.J. Inhibition of the protein kinase PKR by the internal ribosome entry site of hepatitis C virus genomic RNA. RNA 2003, 9, 858-870.
51. Shimoike, T.; McKenna, S.A.; Lindhout, D.A.; Puglisi, J.D. Translational insensitivity to potent activation of PKR by HCV IRES RNA. Antiviral Res. 2009, 83, 228-237.
52. Carpick, B.W.; Graziano, V.; Schneider, D.; Maitra, R.K.; Lee, X.; Williams, B.R. Characterization of the solution complex between the interferon-induced, double-stranded RNAactivated protein kinase and HIV-I trans-activating region RNA. J. Biol. Chem. 1997, 272, 9510-9516.
53. Edery, I.; Petryshyn, R.; Sonenberg, N. Activation of double-stranded RNA-dependent kinase (dsl) by the TAR region of HIV-1 mRNA: A novel translational control mechanism. Cell 1989, 56, 303-312.
54. Maitra, R.K.; McMillan, N.A.; Desai, S.; McSwiggen, J.; Hovanessian, A.G.; Sen, G.; Williams, B.R.; Silverman, R.H. HIV-1 TAR RNA has an intrinsic ability to activate interferon-inducible enzymes. Virology 1994, 204, 823-827.
55. Dauber, B.; Martinez-Sobrido, L.; Schneider, J.; Hai, R.; Waibler, Z.; Kalinke, U.; Garcia-Sastre, A.; Wolff, T. Influenza B virus ribonucleoprotein is a potent activator of the antiviral kinase PKR. PLoS Pathog. 2009, 5, e1000473.
56. Heinicke, L.A.; Wong, C.J.; Lary, J.; Nallagatla, S.R.; Diegelman-Parente, A.; Zheng, X.; Cole, J.L.; Bevilacqua, P.C. RNA dimerization promotes PKR dimerization and activation. J. Mol. Biol. 2009, 390, 319-338.
57. Ben-Asouli, Y.; Banai, Y.; Pel-Or, Y.; Shir, A.; Kaempfer, R. Human interferon-gamma mRNA autoregulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR. Cell 2002, 108, 221-232.
58. Davis, S.; Watson, J.C. In vitro activation of the interferon-induced, double-stranded RNAdependent protein kinase PKR by RNA from the 3' untranslated regions of human alphatropomyosin. Proc. Natl. Acad. Sci. USA 1996, 93, 508-513.
59. Majde, J.A. Viral double-stranded RNA, cytokines, and the flu. J. Interferon Cytokine Res. 2000, 20, 259-272.
60. Palese, P.; Shaw, M. Orthomyxoviridae: The viruses and their replication. In Fields-Virology, 5th ed.; Knipe, D.M., Howley, P.M., Eds.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2007; pp. 1647-1690.
61. Tian, B.; Mathews, M.B. Functional characterization of and cooperation between the doublestranded RNA-binding motifs of the protein kinase PKR. J. Biol. Chem. 2001, 276, 9936-9944.
62. Peters, G.A.; Hartmann, R.; Qin, J.; Sen, G.C. Modular structure of PACT: Distinct domains for binding and activating PKR. Mol. Cell. Biol. 2001, 21, 1908-1920.
63. Marques, J.T.; White, C.L.; Peters, G.A.; Williams, B.R.; Sen, G.C. The role of PACT in mediating gene induction, PKR activation, and apoptosis in response to diverse stimuli. J. Interferon Cytokine Res. 2008, 28, 469-476.
64. Bergmann, M.; Garcia-Sastre, A.; Carnero, E.; Pehamberger, H.; Wolff, K.; Palese, P.; Muster, T. Influenza virus NS1 protein counteracts PKR-mediated inhibition of replication. J. Virol. 2000, 74, 6203-6206.
65. Dauber, B.; Schneider, J.; Wolff, T. Double-stranded RNA binding of influenza B virus nonstructural NS1 protein inhibits protein kinase R but is not essential to antagonize production of alpha/beta interferon. J. Virol. 2006, 80, 11667-11677.
66. Hatada, E.; Saito, S.; Fukuda, R. Mutant influenza viruses with a defective NS1 protein cannot block the activation of PKR in infected cells. J. Virol. 1999, 73, 2425-2433.
67. Dauber, B.; Heins, G.; Wolff, T. The influenza B virus nonstructural NS1 protein is essential for efficient viral growth and antagonizes beta interferon induction. J. Virol. 2004, 78, 1865-1872.
68. Donelan, N.R.; Dauber, B.; Wang, X.; Basler, C.F.; Wolff, T.; Garcia-Sastre, A. The N-and Cterminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3 and beta interferon promoter activation. J. Virol. 2004, 78, 11574-11582.
69. Ludwig, S.; Wang, X.; Ehrhardt, C.; Zheng, H.; Donelan, N.; Planz, O.; Pleschka, S.; Garcia-Sastre, A.; Heins, G.; Wolff, T. The influenza A virus NS1 protein inhibits activation of Jun N-terminal kinase and AP-1 transcription factors. J. Virol. 2002, 76, 11166-11171.
70. Mibayashi, M.; Martinez-Sobrido, L.; Loo, Y.M.; Cardenas, W.B.; Gale, M., Jr.; Garcia-Sastre, A. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J. Virol. 2007, 81, 514-524.
71. Opitz, B.; Rejaibi, A.; Dauber, B.; Eckhard, J.; Vinzing, M.; Schmeck, B.; Hippenstiel, S.; Suttorp, N.; Wolff, T. IFNbeta induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein. Cell. Microbiol. 2007, 9, 930-938.
72. Wang, W.; Riedel, K.; Lynch, P.; Chien, C.Y.; Montelione, G.T.; Krug, R.M. 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 1999, 5, 195-205.
73. Bae, S.H.; Cheong, H.K.; Lee, J.H.; Cheong, C.; Kainosho, M.; Choi, B.S. Structural features of an influenza virus promoter and their implications for viral RNA synthesis. Proc. Natl. Acad. Sci. USA 2001, 98, 10602-10607.
74. Hsu, M.T.; Parvin, J.D.; Gupta, S.; Krystal, M.; Palese, P. Genomic RNAs of influenza viruses are held in a circular conformation in virions and in infected cells by a terminal panhandle. Proc. Natl. Acad. Sci. USA 1987, 84, 8140-8144.
75. Klumpp, K.; Ruigrok, R.W.; Baudin, F. Roles of the influenza virus polymerase and nucleoprotein in forming a functional RNP structure. EMBO J. 1997, 16, 1248-1257.
76. Schmaljohn, C.; Nichol, S. Bunyaviridae: The viruses and their replication. In Fields-Virology, Knipe, D.M., Howley, P.M., Eds.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2007; PP. 1741-1789.
77. Habjan, M.; Pichlmair, A.; Elliott, R.M.; Overby, A.K.; Glatter, T.; Gstaiger, M.; Superti-Furga, G.; Unger, H.; Weber, F. NSs protein of rift valley fever virus induces the specific degradation of the double-stranded RNA-dependent protein kinase. J. Virol. 2009, 83, 4365-4375.
78. Ikegami, T.; Narayanan, K.; Won, S.; Kamitani, W.; Peters, C.J.; Makino, S. Rift Valley fever virus NSs protein promotes post-transcriptional downregulation of protein kinase PKR and inhibits eIF2alpha phosphorylation. PLoS Pathog. 2009, 5, e1000287.
79. Streitenfeld, H.; Boyd, A.; Fazakerley, J.K.; Bridgen, A.; Elliott, R.M.; Weber, F. Activation of PKR by Bunyamwera virus is independent of the viral interferon antagonist NSs. J. Virol. 2003, 77, 5507-5511.
80. Feng, Z.; Cerveny, M.; Yan, Z.; He, B. The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR. J. Virol. 2007, 81, 182-192.
81. Schumann, M.; Gantke, T.; Muhlberger, E. Ebola virus VP35 antagonizes PKR activity through its C-terminal interferon inhibitory domain. J. Virol. 2009, 83, 8993-8997.
82. Stojdl, D.F.; Abraham, N.; Knowles, S.; Marius, R.; Brasey, A.; Lichty, B.D.; Brown, E.G.; Sonenberg, N.; Bell, J.C. The murine double-stranded RNA-dependent protein kinase PKR is required for resistance to vesicular stomatitis virus. J. Virol. 2000, 74, 9580-9585.
83. Habjan, M.; Andersson, I.; Klingstrom, J.; Schumann, M.; Martin, A.; Zimmermann, P.; Wagner, V.; Pichlmair, A.; Schneider, U.; Muhlberger, E.; Mirazimi, A.; Weber, F. Processing of genome 5' termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction. PloS ONE 2008, 3, e2032.
84. Coloma, R.; Valpuesta, J.M.; Arranz, R.; Carrascosa, J.L.; Ortin, J.; Martin-Benito, J. The structure of a biologically active influenza virus ribonucleoprotein complex. PLoS Pathog. 2009, 5, e1000491.
85. Albertini, A.A.; Wernimont, A.K.; Muziol, T.; Ravelli, R.B.; Clapier, C.R.; Schoehn, G.; Weissenhorn, W.; Ruigrok, R.W. Crystal structure of the rabies virus nucleoprotein-RNA complex. Science 2006, 313, 360-363.
86. Green, T.J.; Zhang, X.; Wertz, G.W.; Luo, M. Structure of the vesicular stomatitis virus nucleoprotein-RNA complex. Science 2006, 313, 357-360.
87. Leppert, M.; Rittenhouse, L.; Perrault, J.; Summers, D.F.; Kolakofsky, D. Plus and minus strand leader RNAs in negative strand virus-infected cells. Cell 1979, 18, 735-747.
88. Sanchez, A.; Kiley, M.P.; Holloway, B.P.; Auperin, D.D. Sequence analysis of the Ebola virus genome: Organization, genetic elements, and comparison with the genome of Marburg virus. Virus Res. 1993, 29, 215-240.
89. Plumet, S.; Herschke, F.; Bourhis, J.M.; Valentin, H.; Longhi, S.; Gerlier, D. Cytosolic 5'-triphosphate ended viral leader transcript of measles virus as activator of the RIG I-mediated interferon response. PloS ONE 2007, 2, e279.
90. Bitko, V.; Musiyenko, A.; Bayfield, M.A.; Maraia, R.J.; Barik, S. Cellular La protein shields nonsegmented negative-strand RNA viral leader RNA from RIG-I and enhances virus growth by diverse mechanisms. J. Virol. 2008, 82, 7977-7987.
91. Takeuchi, K.; Komatsu, T.; Kitagawa, Y.; Sada, K.; Gotoh, B. Sendai virus C protein plays a role in restricting PKR activation by limiting the generation of intracellular double-stranded RNA. J. Virol. 2008, 82, 10102-10110.
92. Toth, A. M.; Devaux, P.; Cattaneo, R.; Samuel, C.E. Protein kinase PKR mediates the apoptosis induction and growth restriction phenotypes of C protein-deficient measles virus. J. Virol. 2009, 83, 961-968.
93. Reutter, G.L.; Cortese-Grogan, C.; Wilson, J.; Moyer, S.A. Mutations in the measles virus C protein that up regulate viral RNA synthesis. Virology 2001, 285, 100-109.
94. Gainey, M.D.; Dillon, P.J.; Clark, K.M.; Manuse, M.J.; Parks, G.D. Paramyxovirus-induced shutoff of host and viral protein synthesis: Role of the P and V proteins in limiting PKR activation. J. Virol. 2008, 82, 828-839.
95. Gale, M., Jr.; Katze, M.G. Molecular mechanisms of interferon resistance mediated by viraldirected inhibition of PKR, the interferon-induced protein kinase. Pharmacol. Ther. 1998, 78, 29-46.
96. Garcia, M.A.; Meurs, E.F.; Esteban, M. The dsRNA protein kinase PKR: Virus and cell control. Biochimie 2007, 89, 799-811.
97. Langland, J.O.; Cameron, J. M.; Heck, M.C.; Jancovich, J.K.; Jacobs, B.L. Inhibition of PKR by RNA and DNA viruses. Virus Res. 2006, 119, 100-110.
98. George, C.X.; Li, Z.; Okonski, K.M.; Toth, A.M.; Wang, Y.; Samuel, C.E. Tipping the balance: Antagonism of PKR kinase and ADAR1 deaminase functions by virus gene products. J. Interferon Cytokine Res. 2009, 29, 477-487.
99. Gack, M.U.; Albrecht, R.A.; Urano, T.; Inn, K.S.; Huang, I.C.; Carnero, E.; Farzan, M.; Inoue, S.; Jung, J.U.; Garcia-Sastre, A. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe 2009, 5, 439-449.
100. de la Luna, S.; Fortes, P.; Beloso, A.; Ortin, J. Influenza virus NS1 protein enhances the rate of translation initiation of viral mRNAs. J. Virol. 1995, 69, 2427-2433.
101. Ehrhardt, C.; Wolff, T.; Pleschka, S.; Planz, O.; Beermann, W.; Bode, J.G.; Schmolke, M.; Ludwig, S. Influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate antiapoptotic signaling responses. J. Virol. 2007, 81, 3058-3067.
102. Fortes, P.; Lamond, A.I.; Ortin, J. Influenza virus NS1 protein alters the subnuclear localization of cellular splicing components. J. Gen. Virol. 1995, 76, 1001-1007.
103. Kochs, G.; Garcia-Sastre, A.; Martinez-Sobrido, L. Multiple anti-interferon actions of the influenza A virus NS1 protein. J. Virol. 2007, 81, 7011-7021.
104. Lu, Y.; Qian, X.Y.; Krug, R.M. The influenza virus NS1 protein: A novel inhibitor of pre-mRNA splicing. Genes Dev. 1994, 8, 1817-1828.
105. Min, J.Y.; Krug, R.M. The primary function of RNA binding by the influenza A virus NS1 protein in infected cells: Inhibiting the 2'-5' oligo (A) synthetase/RNase L pathway. Proc. Natl. Acad. Sci. USA 2006, 103, 7100-7105.
106. Park, Y.W.; Katze, M.G. Translational control by influenza virus. Identification of cis-acting sequences and trans-acting factors which may regulate selective viral mRNA translation. J. Biol. Chem. 1995, 270, 28433-28439.
107. Qiu, Y.; Krug, R.M. The influenza virus NS1 protein is a poly(A)-binding protein that inhibits nuclear export of mRNAs containing poly(A). J. Virol. 1994, 68, 2425-2432.
108. Satterly, N.; Tsai, P.L.; van Deursen, J.; Nussenzveig, D.R.; Wang, Y.; Faria, P.A.; Levay, A.; Levy, D.E.; Fontoura, B.M. Influenza virus targets the mRNA export machinery and the nuclear pore complex. Proc. Natl. Acad. Sci. USA 2007, 104, 1853-1858.
109. Hale, B.G.; Randall, R.E.; Ortin, J.; Jackson, D. The multifunctional NS1 protein of influenza A viruses. J. Gen. Virol. 2008, 89, 2359-2376.
110. Yuan, W.; Krug, R.M. Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. EMBO J. 2001, 20, 362-371.
111. Schneider, J.; Dauber, B.; Melen, K.; Julkunen, I.; Wolff, T. Analysis of influenza B Virus NS1 protein trafficking reveals a novel interaction with nuclear speckle domains. J. Virol. 2009, 83, 701-711.
112. Yin, C.; Khan, J.A.; Swapna, G.V.; Ertekin, A.; Krug, R.M.; Tong, L.; Montelione, G.T. Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses. J. Biol. Chem. 2007, 282, 20584-20592.
113. Wang, W.; Krug, R.M. The RNA-binding and effector domains of the viral NS1 protein are conserved to different extents among influenza A and B viruses. Virology 1996, 223, 41-50.
114. Hatada, E.; Fukuda, R. Binding of influenza A virus NS1 protein to dsRNA in vitro. J. Gen. Virol. 1992, 73, 3325-3329.
115. Lu, Y.; Wambach, M.; Katze, M.G.; Krug, R.M. 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 1995, 214, 222-228.
116. Li, S.; Min, J.Y.; Krug, R.M.; Sen, G.C. Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA. Virology 2006, 349, 13-21.
117. Min, J.Y.; Li, S.; Sen, G.C.; Krug, R.M. A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis. Virology 2007, 363, 236-243.
118. Tan, S.L.; Katze, M.G. 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. 1998, 18, 757-766.
119. 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.
120. Goodman, A.G.; Smith, J.A.; Balachandran, S.; Perwitasari, O.; Proll, S.C.; Thomas, M.J.; Korth, M.J.; Barber, G.N.; Schiff, L.A.; Katze, M.G. The cellular protein P58IPK regulates influenza virus mRNA translation and replication through a PKR-mediated mechanism. J. Virol. 2007, 81, 2221-2230.
121. Goodman, A.G.; Fornek, J.L.; Medigeshi, G.R.; Perrone, L.A.; Peng, X.; Dyer, M.D.; Proll, S.C.; Knoblaugh, S.E.; Carter, V.S.; Korth, M.J.; Nelson, J.A.; Tumpey, T.M.; Katze, M.G. P58(IPK): A novel "CIHD" member of the host innate defense response against pathogenic virus infection. PLoS Pathog. 2009, 5, e1000438.
122. Billecocq, A.; Spiegel, M.; Vialat, P.; Kohl, A.; Weber, F.; Bouloy, M.; Haller, O. NSs protein of Rift Valley fever virus blocks interferon production by inhibiting host gene transcription. J. Virol. 2004, 78, 9798-9806.
123. Blakqori, G.; Delhaye, S.; Habjan, M.; Blair, C.D.; Sanchez-Vargas, I.; Olson, K.E.; Attarzadeh-Yazdi, G.; Fragkoudis, R.; Kohl, A.; Kalinke, U.; Weiss, S.; Michiels, T.; Staeheli, P.; Weber, F. La Crosse bunyavirus nonstructural protein NSs serves to suppress the type I interferon system of mammalian hosts. J. Virol. 2007, 81, 4991-4999.
124. Jaaskelainen, K.M.; Kaukinen, P.; Minskaya, E.S.; Plyusnina, A.; Vapalahti, O.; Elliott, R.M.; Weber, F.; Vaheri, A.; Plyusnin, A. Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter. J. Med. Virol. 2007, 79, 1527-1536.
125. Perrone, L.A.; Narayanan, K.; Worthy, M.; Peters, C.J. The S segment of Punta Toro virus (Bunyaviridae, Phlebovirus) is a major determinant of lethality in the Syrian hamster and codes for a type I interferon antagonist. J. Virol. 2007, 81, 884-892.
126. Thomas, D.; Blakqori, G.; Wagner, V.; Banholzer, M.; Kessler, N.; Elliott, R. M.; Haller, O.; Weber, F. Inhibition of RNA polymerase II phosphorylation by a viral interferon antagonist. J. Biol. Chem. 2004, 279, 31471-31477.
127. Black, T.L.; Safer, B.; Hovanessian, A.; Katze, M.G. The cellular 68,000-Mr protein kinase is highly autophosphorylated and activated yet significantly degraded during poliovirus infection: Implications for translational regulation. J. Virol. 1989, 63, 2244-2251.
128. Black, T.L.; Barber, G.N.; Katze, M.G. Degradation of the interferon-induced 68,000-M(r) protein kinase by poliovirus requires RNA. J. Virol. 1993, 67, 791-800.
129. Basler, C.F.; Mikulasova, A.; Martinez-Sobrido, L.; Paragas, J.; Muhlberger, E.; Bray, M.; Klenk, H.D.; Palese, P.; Garcia-Sastre, A. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J. Virol. 2003, 77, 7945-7956.
130. Basler, C.F.; Wang, X.; Muhlberger, E.; Volchkov, V.; Paragas, J.; Klenk, H.D.; Garcia-Sastre, A.; Palese, P., The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc. Natl. Acad. Sci. USA 2000, 97, 12289-12294.
131. Chang, T.H.; Kubota, T.; Matsuoka, M.; Jones, S.; Bradfute, S.B.; Bray, M.; Ozato, K. Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery. PLoS Pathog. 2009, 5, e1000493.
132. Prins, K.C.; Cardenas, W.B.; Basler, C.F. Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1. J. Virol. 2009, 83, 3069-3077.
133. Huang, Y.; Xu, L.; Sun, Y.; Nabel, G.J. The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein. Mol. Cell. 2002, 10, 307-316.
134. Muhlberger, E.; Weik, M.; Volchkov, V.E.; Klenk, H.D.; Becker, S. Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems. J. Virol. 1999, 73, 2333-2342.
135. Reid, S.P.; Cardenas, W.B.; Basler, C.F. Homo-oligomerization facilitates the interferonantagonist activity of the ebolavirus VP35 protein. Virology 2005, 341, 179-189.
136. Cardenas, W.B.; Loo, Y.M.; Gale, M., Jr.; Hartman, A.L.; Kimberlin, C.R.; Martinez-Sobrido, L.; Saphire, E.O.; Basler, C.F. Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling. J. Virol. 2006, 80, 5168-5178.
137. Hartman, A.L.; Towner, J.S.; Nichol, S.T. A C-terminal basic amino acid motif of Zaire ebolavirus VP35 is essential for type I interferon antagonism and displays high identity with the RNA-binding domain of another interferon antagonist, the NS1 protein of influenza A virus. Virology 2004, 328, 177-184.
138. Hartman, A.L.; Bird, B.H.; Towner, J.S.; Antoniadou, Z.A.; Zaki, S.R.; Nichol, S.T. Inhibition of IRF-3 activation by VP35 is critical for the high level of virulence of ebola virus. J. Virol. 2008, 82, 2699-2704.
139. Hartman, A.L.; Ling, L.; Nichol, S.T.; Hibberd, M.L. Whole-genome expression profiling reveals that inhibition of host innate immune response pathways by Ebola virus can be reversed by a single amino acid change in the VP35 protein. J. Virol. 2008, 82, 5348-5358.
140. Cassady, K.A. Human cytomegalovirus TRS1 and IRS1 gene products block the doublestranded-RNA-activated host protein shutoff response induced by herpes simplex virus type 1 infection. J. Virol. 2005, 79, 8707-8715.
141. Child, S.J.; Hakki, M.; de Niro, K.L.; Geballe, A.P. Evasion of cellular antiviral responses by human cytomegalovirus TRS1 and IRS1. J. Virol. 2004, 78, 197-205.
142. Hakki, M.; Geballe, A.P. Double-stranded RNA binding by human cytomegalovirus pTRS1. J. Virol. 2005, 79, 7311-7318.
143. Blankenship, C.A.; Shenk, T. Mutant human cytomegalovirus lacking the immediate-early TRS1 coding region exhibits a late defect. J. Virol. 2002, 76, 12290-12299.
144. Jones, T.R.; Muzithras, V.P. A cluster of dispensable genes within the human cytomegalovirus genome short component: IRS1, US1 through US5, and the US6 family. J. Virol. 1992, 66, 2541-2546.
145. Hakki, M.; Marshall, E.E.; De Niro, K.L.; Geballe, A.P. Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1. J. Virol. 2006, 80, 11817-11826.
146. Chee, M.S.; Bankier, A.T.; Beck, S.; Bohni, R.; Brown, C.M.; Cerny, R.; Horsnell, T.; Hutchison, C.A., 3rd; Kouzarides, T.; Martignetti, J.A.; Preddie, E.; Satchwell, S.C.; Tomlinson, P.; Weston, K.M.; Barrell, B.G. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr. Top. Microbiol. Immunol. 1990, 154, 125-169.
147. Menard, C.; Wagner, M.; Ruzsics, Z.; Holak, K.; Brune, W.; Campbell, A.E.; Koszinowski, U.H. Role of murine cytomegalovirus US22 gene family members in replication in macrophages. J. Virol. 2003, 77, 5557-5570.
148. Valchanova, R.S.; Picard-Maureau, M.; Budt, M.; Brune, W. Murine cytomegalovirus m142 and m143 are both required to block protein kinase R-mediated shutdown of protein synthesis. J. Virol. 2006, 80, 10181-10190.
149. Child, S.J.; Geballe, A.P. Binding and relocalization of protein kinase R by murine cytomegalovirus. J. Virol. 2009, 83, 1790-1799.
150. Child, S.J.; Hanson, L.K.; Brown, C.E.; Janzen, D.M.; Geballe, A.P. Double-stranded RNA binding by a heterodimeric complex of murine cytomegalovirus m142 and m143 proteins. J. Virol. 2006, 80, 10173-10180.
151. Elde, N.C.; Child, S.J.; Geballe, A.P.; Malik, H.S. Protein kinase R reveals an evolutionary model for defeating viral mimicry. Nature 2009, 457, 485-489.
152. Rothenburg, S.; Seo, E.J.; Gibbs, J.S.; Dever, T.E.; Dittmar, K. Rapid evolution of protein kinase PKR alters sensitivity to viral inhibitors. Nat. Struct. Mol. Biol. 2009, 16, 63-70.