Alpha/beta interferons regulate murine gammaherpesvirus latent gene expression and reactivation from latency

Journal of Virology

Volumn 79, Issue 22, 2005, Pages 14149-14160

  Barton, Erik S ^a   Lutzke, Mary L ^b,c   Rochford, Rosemary ^b   Virgin IV, Herbert W ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b State University of New York Upstate Medical University: College of Medicine   (United States)

^c Kent County Health Department   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; BETA INTERFERON;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELLULAR IMMUNITY; CONTROLLED STUDY; GAMMA 2 HERPES VIRUS; GENE CONTROL; GENE EXPRESSION REGULATION; HERPES VIRUS; IMMUNE RESPONSE; IN VIVO STUDY; LATENT VIRUS INFECTION; M2 GENE; MOUSE; MURINE GAMMAHERPES VIRUS 68; NONHUMAN; PERITONEUM CELL; PRIORITY JOURNAL; PROTEIN FUNCTION; SPLEEN CELL; UPREGULATION; VIRUS CELL INTERACTION; VIRUS GENE; VIRUS INFECTION; VIRUS INHIBITION; VIRUS PATHOGENESIS; VIRUS REACTIVATION; VIRUS STRAIN; WILD TYPE;

ANIMALS; GAMMAHERPESVIRINAE; GENE EXPRESSION REGULATION, VIRAL; HERPESVIRIDAE INFECTIONS; INTERFERON-ALPHA; INTERFERON-BETA; LIVER; LUNG; MICE; MICE, KNOCKOUT; RECEPTORS, INTERFERON; SPLEEN; VIRUS LATENCY; VIRUS REPLICATION;

ANIMALIA; HERPESVIRIDAE; MURINAE;

EID: 27644558111     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.79.22.14149-14160.2005     Document Type: Article

References (105)

1. Agnello, D., C. S. R, Lankford, J. Bream, A. Morinobu, M. Gadina, J. J. O'Shea, and D. M. Frucht. 2003. Cytokines and transcription factors that regulate T helper cell differentiation: new players and new insights. J. Clin. Immunol. 23:147-161.
2. Ahn, J. W, K. L. Powell, P. Kellam, and D. G. Alber. 2002. Gammaherpesvirus lytic gene expression as characterized by DNA array. J. Virol. 76:6244-6256.
3. Arico, E., K. A. Robertson, F. Belardelli, M. Ferrantini, and A. A. Nash. 2004. Vaccination with inactivated murine gammaherpesvirus 68 strongly limits viral replication and latency and protects type I IFN receptor knockout mice from a lethal infection. Vaccine 22:1433-1440.
4. Barnes, B., B. Lubyova, and P. M. Pitha. 2002. On the role of IRF in host defense. J. Interferon Cytokine Res. 22:59-71.
5. Belardelli, F., F. Vignaux, E. Proietti, and I. Gresser. 1984. Injection of mice with antibody to interferon renders peritoneal macrophages permissive for vesicular stomatitis virus and encephalomyocarditis virus. Proc. Natl. Acad. Sci. USA 81:602-606.
6. Biron, C. A. 2001. Interferons alpha and beta as immune regulators-a new look. Immunity 14:661-664.
7. Biron, C. A., K. B. Nguyen, G. C. Pien, L. P. Cousens, and T. P. Salazar-Mather. 1999. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu. Rev. Immunol. 17:189-220.
8. + T-cell response controls productive and latent gammaherpesvirus infection. J. Virol. 79:2573-2583.
9. Burysek, L., W. S. Yeow, and P. M. Pitha. 1999. Unique properties of a second human herpesvirus 8-encoded interferon regulatory factor (vIRF-2). J. Hum. Virol. 2:19-32.
10. + T cells. J. Exp. Med. 184:863-871.
11. Cella, M., D. Jarrossay, F. Facchetti, O. Alebardi, H. Nakajima, A. Lanzavecchia, and M. Colonna. 1999. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat. Med. 5:919-923.
12. Chang, J., R. Renne, D. Dittmer, and D. Ganem. 2000. Inflammatory cytokines and the reactivation of Kaposi's sarcoma-associated herpesvirus lytic replication. Virology 266:17-25.
13. Chatterjee, M., J. Osborne, G. Bestetti, Y. Chang, and P. S. Moore. 2002. Viral IL-6-induced cell proliferation and immune evasion of interferon activity. Science 298:1432-1435.
14. Chong, K. T., I. Gresser, and C. A. Mims. 1983. Interferon as a defense mechanism in mouse cytomegalovirus infection. J. Gen. Virol. 64:461-464.
15. + T cell-mediated control of a gamma-herpesvirus in B cell-deficient mice is mediated by IFN-gamma. Proc. Natl. Acad. Sci. USA 96:5135-5140.
16. Clambey, E. T., H. W. Virgin, and S. H. Speck. 2000. Disruption of the murine gammaherpesvirus 68 M1 open reading frame leads to enhanced reactivation from latency. J. Virol. 74:1973-1984.
17. Clambey, E. T., H. W. Virgin, and S. H. Speck. 2002. Characterization of a spontaneous 9.5-kilobase-deletion mutant of murine gammaherpesvirus 68 reveals tissue-specific genetic requirements for latency. J. Virol. 76:6532-6544.
18. Coccia, E. M., G. Romeo, A. Nissim, G. Marziali, R. Albertini, E. Affabris, A. Battistini, G. Fiorucci, R. Orsatti, and G. B. Rossi. 1990. A full-length murine 2-5A synthetase cDNA transfected in NIH-3T3 cells impairs EMCV but not VSV replication. Virology 179:228-233.
19. Colonna, M., G. Trinchieri, and Y. J. Liu. 2004. Plasmacytoid dendritic cells in immunity. Nat. Immunol. 5:1219-1226.
20. Dal Canto, A. J., P. E. Swanson, A. K. O'Guin, S. H. Speck, and H. W. Virgin. 2001. IFN-gamma action in the media of the great elastic arteries, a novel immunoprivileged site. J. Clin. Investig. 107:R15-R22.
21. Dal Canto, A. J., H. W. Virgin, and S. H. Speck. 2000. Ongoing viral replication is required for gammaherpesvirus 68-induced vascular damage. J. Virol. 74:11304-11310.
22. Dunn, G. P., A. T. Bruce, K. C. Sheehan, V. Shankaran, R. Uppalurl, J. D. Bui, M. S. Diamond, C. M. Koebel, C. Arthur, J. M. White, and R. D. Schreiber. 2005. A critical function for type I interferons in cancer immunoediting. Nat. Immunol. 6:722-729.
23. Durand, V., S. Y. Wong, D. F. Tough, and A. Le Bon. 2004. Shaping of adaptive immune responses to soluble proteins by TLR agonists: a role for IFN-alpha/beta. Immunol. Cell Biol. 82:596-602.
24. Dutia, B. M., D. J. Allen, H. Dyson, and A. A. Nash. 1999. Type I interferons and IRF-1 play a critical role in the control of a gammaherpesvirus infection. Virology 261:173-179.
25. Ebrahimi, B., B. M. Dutia, K. L. Roberts, J. J. Garcia-Ramirez, P. Dickinson, J. P. Stewart, P. Ghazal, D. J. Roy, and A. A. Nash. 2003. Transcriptome profile of murine gammaherpesvirus-68 lytic infection. J. Gen. Virol. 84:99-109.
26. Fiette, L., C. Aubert, U. Muller, S. Huang, M. Aguet, M. Brahic, and J.-F. Bureau. 1995. Theiler's virus infection of 129SV mice that lack the interferon α/β or interferon gamma receptors. J. Exp. Med. 181:2069-2076.
27. Flano, E., Q. Jia, J. Moore, D. L. Woodland, R. Sun, and M. A. Blackman. 2005. Early establishment of gamma-herpesvirus latency: implications for immune control. J. Immunol. 174:4972-4978.
28. + T cell activation associated with latent murine gammaherpesvirus infection. J. Immunol. 163:3403-3408.
29. + T cells during long-term gammaherpesvirus infection. J. Virol. 75:7744-7748.
30. Gangappa, S., S. B. Kapadia, S. H. Speck, and H. W. Virgin. 2002. Antibody to a lytic cycle viral protein decreases gammaherpesvirus latency in B-cell-deficient mice. J. Virol. 76:11460-11468.
31. Gao, S. J., C. Boshoff, S. Jayachandra, R. A. Weiss, Y. Chang, and P. S. Moore. 1997. KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway. Oncogene 15:1979-1985.
32. Gil, M. P., E. Bohn, A. K. O'Guin, C. V. Ramana, B. Levine, G. R. Stark, H. W. Virgin, and R. D. Schreiber. 2001. Biologic consequences of Stat1-independent IFN signaling. Proc. Natl. Acad. Sci. USA 98:6680-6685.
33. Gresser, I., M. G. Tovey, M.-T. Bandu, C. Maury, and D. Brouty-Boye. 1976. Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomyocarditis virus infection. J. Exp. Med. 144:1305-1315.
34. Hamilton-Easton, A. M., J. P. Christensen, and P. C. Doherty. 1999. Turnover of T cells in murine gammaherpesvirus 68-infected mice. J. Virol. 73:7866-7869.
35. + T cells from young and old mice. J. Immunol. 150: 3602-3614.
36. Honda, K., Y. Ohba, H. Yanai, H. Negishi, T. Mizutani, A. Takaoka, C. Taya, and T. Taniguchi. 2005. Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 434:1035-1040.
37. Honda, K., H. Yanai, H. Negishi, M. Asagiri, M. Sato, T. Mizutani, N. Shimada, Y. Ohba, A. Takaoka, N. Yoshida, and T. Taniguchi. 2005. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434:772-777.
38. Hwang, S. Y., P. J. Hertzog, K. A. Holland, S. H. Sumarsono, M. J. Tymms, J. A. Hamilton, G. Whitty, I. Bertoncello, and J. Kola. 1995. A null mutation in the gene encoding a type I interferon receptor component eliminates antiproliferative and antiviral responses to interferons alpha and beta and alters macrophage responses. Proc. Natl. Acad. Sci. USA 92:11284-11288.
39. Jacoby, M. A., H. W. Virgin, and S. H. Speck. 2002. Disruption of the M2 gene of murine gammaherpesvirus 68 alters splenic latency following intranasal, but not intraperitoneal, inoculation. J. Virol. 76:1790-1801.
40. Jonjic, S., I. Pane, B. Polic, I. Crnkovic, P. Lucin, and U. H. Koszinowski. 1994. Antibodies are not essential for the resolution of primary cytomegalovirus infection but limit dissemination of recurrent virus. J. Exp. Med. 179:1713-1717.
41. Kapadia, S. B., B. Levine, S. H. Speck, and H. W. Virgin. 2002. Critical role of complement and viral evasion of complement in acute, persistent, and latent gamma-herpesvirus infection. Immunity 17:143-155.
42. Khabar, K. S., M. Dhalla, Y. Siddiqui, A. Zhou, M. N. Al Ahdal, S. D. Der, R. H. Silverman, and B. R. Williams. 2000. Effect of deficiency of the double-stranded RNA-dependent protein kinase, PKR, on antiviral resistance in the presence or absence of ribonuclease L: HSV-1 replication is particularly sensitive to deficiency of the major IFN-mediated enzymes. J. Interferon Cytokine Res. 20;653-659.
43. Kim, I. J., E. Flano, D. L. Woodland, and M. A. Blackman. 2002. Antibody-mediated control of persistent γ-herpesvirus infection. J. Immunol. 168: 3958-3964.
44. Kim, I. J., E. Flano, D. L. Woodland, F. E. Lund, T. D. Randall, and M. A. Blackman, 2003. Maintenance of long term gamma-herpesvirus B cell latency is dependent on CD40-mediated development of memory B cells. J. Immunol. 171:886-892.
45. + T cells stimulated by virus-induced type I interferon. Nat. Immunol. 4:1009-1015.
46. Leib, D. A. 2002. Counteraction of interferon-induced antiviral responses by herpes simplex viruses. Curr. Top. Microbiol. Immunol. 269:171-185.
47. Leib, D. A., T. E. Harrison, K. M. Laslo, M. A. Machalek, N. J. Moorman, and H. W. Virgin. 1999. Interferons regulate the phenotype of wild-type and mutant herpes simplex viruses in vivo. J. Exp. Med. 189:663-672.
48. 47a. Lenschow, D. J., N. V. Giannakopoulos, L. J. Gunn, C. Johnston, A. K. O'Guin, R. E. Schmidt, B. Levine, and H. W. Virgin IV. 2005. Identification of interferon-stimulated gene 15 as an antiviral molecule during Sindbis virus infection in vivo. J. Virol 79:13974-13983.
49. Li, X. L., J. A. Blacktord, and B, A. Hassel. 1998. RNase L mediates the antiviral effect of interferon through a selective reduction in viral RNA during encephalomyocarditis virus infection. J. Virol. 72:2752-2759.
50. Liang, X. Z., Y. C. Shin, R. E. Means, and J. U. Jung. 2004. Inhibition of interferon-mediated antiviral activity by murine gammaherpesvirus 68 latency-associated M2 protein. J. Virol. 78:12416-12427.
51. Loh, J., D. A. Thomas, P. A. Revell, T. J. Ley, and H. W. Virgin. 2004. Granzymes and caspase 3 play important roles in control of gammaherpesvirus latency. J. Virol. 78:12519-12528.
52. Lubyova, B., M. J. Kellum, A. J. Frisancho, and P. M. Pitha. 2004. Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 stimulates the transcriptional activity of cellular IRF-3 and IRF-7. J. Biol. Chem. 279:7643-7654.
53. Marrack, P., J. Kappler, and T. Mitchell. 1999. Type I interferons keep activated T cells alive. J. Exp. Med. 189:521-529.
54. Martinez-Guzman, D., T. Rickabaugh, T. T. Wu, H. Brown, S. Cole, M. J. Song, L. Tong, and R. Sun. 2003. Transcription program of murine gammaherpesvirus 68. J. Virol. 77:10488-10503.
55. McClellan, J. S., S. A. Tibbetts, S. Gangappa, K. A. Brett, and H. W. Virgin. 2004. Critical role of CD4 T cells in an antibody-independent mechanism of vaccination against gamma-herpesvirus latency. J. Virol. 78:6836-6845.
56. Means, R. E., J. K. Choi, H. Nakamura, Y. H. Chung, S. Ishido, and J. U. Jung. 2002. Immune evasion strategies of Kaposi's sarcoma-associated herpesvirus. Curr. Top. Microbiol. Immunol. 269:187-201.
57. Meraz, M. A., J. M. White, K. C. F. Sheehan, E. A. Bach, S. J. Rodig, A. S. Dighe, D. H. Kaplan, J. K. Riley, A. C. Greenlund, D. Campbell, K. Carver-Moore, R. N. DuBois, R. Clark, M. Aguet, and R. D. Schreiber. 1996. Targeted disruption of the Stat 1 gene in mice reveals unexpected physiologic specificity of the JAK-STAT signalling pathway. Cell 84:431-442.
58. Monini, P., F. Carlini, M. Stürzl, P. Rimessi, F. Superti, M. Franco, G. Melucci-Vigo, A. Cafaro, D. Goletti, C. Sgadari, S. Butto', P. Leone, P. Leone, C. Chiozzini, C. Barresi, A. Tinari, A. Bonaccorsi, M. R. Capobianchi, M. Giuliani, A. di Carlo, M. Andreoni, G. Rezza, and B. Ensoli. 1999. Alpha interferon inhibits human herpesvirus 8 (HHV-8) reactivation in primary effusion lymphoma cells and reduces HHV-8 load in cultured peripheral blood mononuclear cells. J. Virol. 73:4029-4041.
59. Mossman, K. L. 2002. Activation and inhibition of virus and interferon: the herpesvirus story. Viral Immunol. 15:3-15.
60. Muller, U., S. Steinhoff, L. F. L. Reis, S. Hemmi, J. Pavlovic, R. M. Zinkernagel, and M. Aguet. 1994. Functional role of type I and type II interferons in antiviral defense. Science 264:1918-1921.
61. Nguyen, K. B., W. T. Watford, R. Salomon, S. R. Hofmann, G. C. Pien, A. Morinobu, M. Gadina, J. J. O'Shea, and C. A. Biron. 2002. Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection. Science 297:2063-2066.
62. Ning, S., A. M. Hahn, L. E. Huye, and J. S. Pagano. 2003. Interferon regulatory factor 7 regulates expression of Epstein-Barr virus latent membrane protein 1: a regulatory circuit. J. Virol. 77:9359-9368.
63. Ou, R., S. Zhou, L. Huang, and D. Moskophidis. 2001. Critical role for alpha/ beta and gamma interferons in persistence of lymphocytic choriomeningitis virus by clonal exhaustion of cytotoxic T cells. J. Virol. 75:8407-8423.
64. Parravinci, C, M. Corbellino, M. Paulli, U. Magrini, M. Lazzarino, P. S. Moore, and Y. Chang. 1997. Expression of a virus-derived cytokine, KSHV vIL-6, in HIV-seronegative Castleman's disease. Am. J. Pathol. 151:1517-1522.
65. Player, M. R., and P. F. Torrence. 1998. The 2-5A system: modulation of viral and cellular processes through acceleration of RNA degradation. Pharmacol. Ther. 78:55-113.
66. Rivas, C., A. E. Thlick, C. Parravicini, P. S. Moore, and Y. Chang. 2001. Kaposi's sarcoma-associated herpesvirus LANA2 is a B-cell-specific latent viral protein that inhibits p53. J. Virol. 75:429-438.
67. Rochford, R., M. L. Lutzke, R. S. Alfinito, A. Clavo, and R. D. Cardin. 2001. Kinetics of murine gammaherpesvirus 68 gene expression following infection of murine cells in culture and in mice. J. Virol. 75:4955-4963.
68. Ryman, K. D., L. J. White, R. E. Johnston, and W. B. Klimstra. 2002. Effects of PKR/RNase L-dependent and alternative antiviral pathways on alphavirus replication and pathogenesis. Viral Immunol. 15:53-76.
69. Samuel, C. E. 1991. Antiviral actions of interferon. Interferon-regulated cellular proteins and their surprisingly selective antiviral activities. Virology 183:1-11.
70. Santini, S. M., C. Lapenta, M. Logozzi, S. Parlato, M. Spada, T. Di Pucchio, and F. Belardelli. 2000. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J. Exp. Med. 191:1777-1788.
71. Sarawar, S. R., R. D. Cardin, J. W. Brooks, M. Mehrpooya, A. M. Hamilton-Easton, X. Y. Mo, and P. C. Doherty. 1997. Gamma interferon is not essential for recovery from acute infection with murine gammaherpesvirus 68. J. Virol. 71:3916-3921.
72. Sarawar, S. R., B. J. Lee, S. K. Reiter, and S. P. Schoenberger. 2001. Stimulation via CD40 can substitute for CD4 T cell function in preventing reactivation of a latent herpesvirus. Proc. Natl. Acad. Sci. USA 98:6325-6329.
73. Sen, G. C. 2001. Viruses and interferons. Annu. Rev. Microbiol. 55:255-281.
74. Sparks-Thissen, R. L., D. C. Braaten, S. Kreher, S. H. Speck, and H. W. Virgin. 2004. An optimized CD4 T-cell response can control productive and latent gammaherpesvirus infection. J. Virol. 78:6827-6835.
75. Speck, S. H., and H. W. Virgin. 1999. Host and viral genetics of chronic infection: a mouse model of gamma-herpesvirus pathogenesis. Curr. Opin. Microbiol. 2:403-409.
76. Stark, G. R., I. M. Kerr, B. R. Williams, R. H. Silverman, and R. D. Schreiber. 1998. How cells respond to interferons. Annu. Rev. Biochem. 67:227-264.
77. 75a. Steed, A., E. S. Barton, S. A. Tibbetts, D. L. Popkin, M. L. Lutzke, R. Rochford, and H. W. Virgin IV. Gamma interferon blocks gammaherpesvirus reactivation from latency. J. Virol., in press.
78. + T cell response during acute and persistent murine gamma-herpesvirus infection. Eur. J. Immunol. 29: 1059-1067.
79. Stevenson, P. G., and P. C. Doherty. 1998. Kinetic analysis of the specific host response to a murine gammaherpesvirus. J. Virol. 72:943-949.
80. Taniguchi, T., and A. Takaoka. 2001. A weak signal for strong responses: interferon-alpha/beta revisited. Nat. Rev. Mol. Cell Biol. 2:378-386.
81. 78a. Tarakanova, V. L., F. Suarez, S. A. Tibbetts, M. A. Jacoby, K. E. Week, J. L. Hess, S. H. Speck, and H. W. Virgin IV. Murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in BALB 2 microglobulin-deficient mice. J. Virol., in press.
82. Tibbetts, S. A., J. Loh, V. van Berkel, J. S. McClellan, M. A. Jacoby, S. B. Kapadia, S. H. Speck, and H. W. Virgin. 2003. Establishment and maintenance of gammaherpesvirus latency are independent of infective dose and route of infection. J. Virol. 77:7696-7701.
83. Tibbetts, S. A., L. Van Dyk, S. H. Speck, and H. W. Virgin. 2002. Immune control of the number and reactivation phenotype of cells latently infected with a gammaherpesvirus. J. Virol. 76:7125-7132.
84. + T cell control and morbidity. J. Gen. Virol. 82:1971-1981.
85. Van Den Broek, M. F., U. Muller, S. Huang, M. Aguet, and R. M. Zinkernagel. 1995. Antiviral defense in mice lacking both alpha/beta and gamma interferon receptors. J. Virol. 69:4792-4796.
86. Van Dyk, L. F., H. W. Virgin, and S. H. Speck. 2000. The murine gammaherpesvirus 68 v-cyclin is a critical regulator of reactivation from latency. J. Virol. 74:7451-7461.
87. Van Dyk, L. F., H. W. Virgin, and S. H. Speck. 2003. Maintenance of gammaherpesvirus latency requires viral cyclin in the absence of B lymphocytes. J. Virol. 77:5118-5126.
88. Virgin, H. W., P. Latreille, P. Wamsley, K. Hallsworth, K. E. Weck, A. J. Dal Canto, and S. H. Speck. 1997. Complete sequence and genomic analysis of murine gammaherpesvirus 68. J. Virol. 71:5894-5904.
89. Virgin, H. W., R. M. Presti, X.-Y. Li, C. Liu, and S. H. Speck. 1999. Three distinct regions of the murine gammaherpesvirus 68 genome are transcriptionally active in latently infected mice. J. Virol. 73:2321-2332.
90. Virgin, H. W., and S. H. Speck. 1999. Unraveling immunity to gammaherpesviruses: a new model for understanding the role of immunity in chronic virus infection. Curr. Opin. Immunol. 11:371-379.
91. Wang, J., J. Zhang, L. Zhang, W. Harrington, Jr., J. T. West, and C. Wood. 2005. Modulation of human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus replication and transcription activator transactivation by interferon regulatory factor 7. J. Virol. 79:2420-2431.
92. Week, K. E., M. L. Barkon, L. I. Yoo, S. H. Speck, and H. W. Virgin. 1996. Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68. J. Virol. 70:6775-6780.
93. Week, K. E., A. J. Dal Canto, J. D. Gould, A. K. O'Guin, K. A. Roth, J. E. Saffitz, S. H. Speck, and H. W. Virgin. 1997. Murine gammaherpesvirus 68 causes severe large vessel arteritis in mice lacking interferon-gamma responsiveness: a new model for virus induced vascular disease. Nat. Med. 3:1346-1353.
94. Week, K. E., S. S. Kim, H. W. Virgin, and S. H. Speck. 1999. B cells regulate murine gammaherpesvirus 68 latency. J. Virol. 73:4651-4661.
95. Week, K. E., S. S. Kim, H. W. Virgin, and S. H. Speck. 1999. Macrophages are the major reservoir of latent murine gammaherpesvirus 68 in peritoneal cells. J. Virol. 73:3273-3283.
96. Williams, B. R. 1999. PKR; a sentinel kinase for cellular stress. Oncogene 18:6112-6120.
97. Wu, W., R. Rochford, L. Toomey, W. Harrington, Jr., and G. Feuer. 2005. Inhibition of HHV-8/KSHV infected primary effusion lymphomas in NOD/ SCID mice by azidothymidine and interferon-alpha. Leuk. Res. 29:545-555.
98. Yu, Y., S. E. Wang, and G. S. Hayward. 2005. The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation. Immunity 22:59-70.
99. Zhang, J., S. C. Das, C. Kotalik, A. K. Pattnaik, and L. Zhang. 2004. The latent membrane protein 1 of Epstein-Barr virus establishes an antiviral state via induction of interferon-stimulated genes. J. Biol. Chem. 279: 46335-46342.
100. Zhang, L., and J. S. Pagano. 1997. IRF-7, a new interferon regulatory factor associated with Epstein-Barr virus latency. Mol. Cell. Biol. 17:5748-5757.
101. Zhang, L., and J. S. Pagano. 2001. Interferon regulatory factor 7: a key cellular mediator of LMP-1 in EBV latency and transformation. Semin. Cancer Biol. 11:445-453.
102. Zheng, X., R. H. Silverman, A. Zhou, T, Goto, B. S. Kwon, H. E. Kaufman, and J. M. Hill. 2001. Increased severity of HSV-1 keratitis and mortality in mice lacking the 2-5A-dependent RNase L gene. Investig. Ophthalmol. Vis. Sci. 42:120-126.
103. Zhou, A., J. M. Paranjape, S. D. Der, B. R. Williams, and R. H. Silverman. 1999. Interferon action in triply deficient mice reveals the existence of alternative antiviral pathways. Virology 258:435-440.
104. Zhu, F. X., S. M. King, E. J. Smith, D. E. Levy, and Y. Yuan. 2002. A Kaposi's sarcoma-associated herpesviral protein inhibits virus-mediated induction of type I interferon by blocking IRF-7 phosphorylation and nuclear accumulation. Proc. Natl. Acad. Sci. USA 99:5573-5578.
105. Zimring, J. C., S. Goodbourn, and M. K. Offermann. 1998. Human herpesvirus 8 encodes an interferon regulatory factor (IRF) homolog that represses IRF-1-mediated transcription. J. Virol. 72:701-707.