Immunologic Research

, Volume 48, Issue 1–3, pp 122–146 | Cite as

Prospects of a novel vaccination strategy for human gamma-herpesviruses

Article

Abstract

Due to the oncogenic potential associated with persistent infection of human gamma-herpesviruses, including Epstein–Barr virus (EBV or HHV-4) and Kaposi’s sarcoma-associated herpesvirus (KSHV or HHV-8), vaccine development has focused on subunit vaccines. However, the results using an animal model of mouse infection with a related rodent virus, murine gamma-herpesvirus 68 (MHV-68, γHV-68, or MuHV-4), have shown that the only effective vaccination strategy is based on live attenuated viruses, including viruses engineered to be incapable of establishing persistence. Vaccination with a virus lacking persistence would eliminate many potential complications. Progress in understanding persistent infections of EBV and KSHV raises the possibility of engineering a live attenuated virus without persistence. Therefore, we should keep the option open for developing a live EBV or KSHV vaccine.

Keywords

Gamma-herpesviruses Vaccine EBV KSHV MHV-68 

References

  1. 1.
    Sokal EM, et al. Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults. J Infect Dis. 2007;196(12):1749–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Jia Q, et al. Induction of protective immunity against murine gammaherpesvirus 68 infection in the absence of viral latency. J Virol. 2010;84(5):2453–65.PubMedCrossRefGoogle Scholar
  3. 3.
    Stoopler ET. Oral herpetic infections (HSV 1–8). Dent Clin North Am. 2005;49(1):15–29. vii.PubMedCrossRefGoogle Scholar
  4. 4.
    Levy JA. Three new human herpesviruses (HHV6, 7, and 8). Lancet. 1997;349(9051):558–63.PubMedCrossRefGoogle Scholar
  5. 5.
    Rickinson AB, Kieff E. Epstein-Barr virus. In: Knipe DM, Howley PM, editors. Fields virology. Philadelphia: Lippincott Williams and Wilkins; 2001. p. 2575–628.Google Scholar
  6. 6.
    Roizman B, Pellet PE. The family herpesviridae: a brief introduction. In: Knipe DM, Howley PM, editors. Fields virology. Philadephia: Lippincott Williams & Wilkins; 2001. p. 2381–98.Google Scholar
  7. 7.
    Pass RF. Cytomegalovirus. In: Knipe DM, Howley PM, editors. Fields virology. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 2675–706.Google Scholar
  8. 8.
    Cesarman E, et al. Kaposi’s sarcoma-associated herpesvirus in non-AIDS related lymphomas occurring in body cavities. Am J Pathol. 1996;149(1):53–7.PubMedGoogle Scholar
  9. 9.
    Chang Y, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science. 1994;266(5192):1865–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Brambilla L, et al. HHV8 cell-associated viraemia and clinical presentation of Mediterranean Kaposi’s sarcoma. Lancet. 1996;347(9011):1338.PubMedCrossRefGoogle Scholar
  11. 11.
    Corbellino M, et al. The role of human herpesvirus 8 and Epstein-Barr virus in the pathogenesis of giant lymph node hyperplasia (Castleman’s disease). Clin Infect Dis. 1996;22(6):1120–1.PubMedGoogle Scholar
  12. 12.
    Corbellino M, et al. Restricted tissue distribution of extralesional Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS patients with Kaposi’s sarcoma. AIDS Res Hum Retroviruses. 1996;12(8):651–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Soulier J, et al. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood. 1995;86(4):1276–80.PubMedGoogle Scholar
  14. 14.
    Dedicoat M, Newton R. Review of the distribution of Kaposi’s sarcoma-associated herpesvirus (KSHV) in Africa in relation to the incidence of Kaposi’s sarcoma. Br J Cancer. 2003;88(1):1–3.PubMedCrossRefGoogle Scholar
  15. 15.
    Wabinga HR, et al. Trends in cancer incidence in Kyadondo County, Uganda, 1960–1997. Br J Cancer. 2000;82(9):1585–92.PubMedCrossRefGoogle Scholar
  16. 16.
    Bassett MT, et al. Cancer in the African population of Harare, Zimbabwe, 1990–1992. Int J Cancer. 1995;63(1):29–36.PubMedCrossRefGoogle Scholar
  17. 17.
    Mbulaiteye SM, et al. Spectrum of cancers among HIV-infected persons in Africa: the Uganda AIDS-Cancer Registry Match Study. Int J Cancer. 2006;118(4):985–90.PubMedCrossRefGoogle Scholar
  18. 18.
    Efstathiou S, Ho YM, Minson AC. Cloning and molecular characterization of the murine herpesvirus 68 genome. J Gen Virol. 1990;71(Pt 6):1355–64.PubMedCrossRefGoogle Scholar
  19. 19.
    Virgin HWt, et al. Complete sequence and genomic analysis of murine gammaherpesvirus 68. J Virol. 1997;71(8):5894–904.PubMedGoogle Scholar
  20. 20.
    Mackett M, et al. Genetic content and preliminary transcriptional analysis of a representative region of murine gammaherpesvirus 68. J Gen Virol. 1997;78(Pt 6):1425–33.PubMedGoogle Scholar
  21. 21.
    Sunil-Chandra NP, et al. Virological and pathological features of mice infected with murine gamma-herpesvirus 68. J Gen Virol. 1992;73(Pt 9):2347–56.PubMedCrossRefGoogle Scholar
  22. 22.
    Doherty PC, et al. Tuning into immunological dissonance: an experimental model for infectious mononucleosis. Curr Opin Immunol. 1997;9(4):477–83.PubMedCrossRefGoogle Scholar
  23. 23.
    Tripp RA, et al. Pathogenesis of an infectious mononucleosis-like disease induced by a murine gamma-herpesvirus: role for a viral superantigen? J Exp Med. 1997;185(9):1641–50.PubMedCrossRefGoogle Scholar
  24. 24.
    Sunil-Chandra NP, et al. Lymphoproliferative disease in mice infected with murine gammaherpesvirus 68. Am J Pathol. 1994;145(4):818–26.PubMedGoogle Scholar
  25. 25.
    Tarakanova VL, et al. Murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in BALB beta2 microglobulin-deficient mice. J Virol. 2005;79(23):14668–79.PubMedCrossRefGoogle Scholar
  26. 26.
    Lee KS, et al. Murine gammaherpesvirus 68 infection of IFNgamma unresponsive mice: a small animal model for gammaherpesvirus-associated B-cell lymphoproliferative disease. Cancer Res. 2009;69(13):5481–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Lau R, Middeldorp J, Farrell PJ. Epstein-Barr virus gene expression in oral hairy leukoplakia. Virology. 1993;195(2):463–74.PubMedCrossRefGoogle Scholar
  28. 28.
    Katano H, et al. Expression and localization of human herpesvirus 8-encoded proteins in primary effusion lymphoma, Kaposi’s sarcoma, and multicentric Castleman’s disease. Virology. 2000;269(2):335–44.PubMedCrossRefGoogle Scholar
  29. 29.
    Staskus KA, et al. Cellular tropism and viral interleukin-6 expression distinguish human herpesvirus 8 involvement in Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. J Virol. 1999;73(5):4181–7.PubMedGoogle Scholar
  30. 30.
    Sun R, et al. Kinetics of Kaposi’s sarcoma-associated herpesvirus gene expression. J Virol. 1999;73(3):2232–42.PubMedGoogle Scholar
  31. 31.
    Nicholas J, et al. Kaposi’s sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6. Nat Med. 1997;3(3):287–92.PubMedCrossRefGoogle Scholar
  32. 32.
    Cannon JS, et al. Heterogeneity of viral IL-6 expression in HHV-8-associated diseases. J Infect Dis. 1999;180(3):824–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Molden J, et al. A Kaposi’s sarcoma-associated herpesvirus-encoded cytokine homolog (vIL-6) activates signaling through the shared gp130 receptor subunit. Journal of Biological Chemistry. 1997;272(31):19625–31.PubMedCrossRefGoogle Scholar
  34. 34.
    Jones KD, et al. Involvement of interleukin-10 (IL-10) and viral IL-6 in the spontaneous growth of Kaposi’s sarcoma herpesvirus-associated infected primary effusion lymphoma cells. Blood. 1999;94(8):2871–9.PubMedGoogle Scholar
  35. 35.
    Chang J, et al. Inflammatory cytokines and the reactivation of Kaposi’s sarcoma- associated herpesvirus lytic replication. Virology. 2000;266(1):17–25.PubMedCrossRefGoogle Scholar
  36. 36.
    An J, et al. Kaposi’s sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: the role of the NF-kappaB and JNK/AP1 pathways. Oncogene. 2003;22(22):3371–85.PubMedCrossRefGoogle Scholar
  37. 37.
    Nicholas J, et al. A single 13-kilobase divergent locus in the Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genome contains nine open reading frames that are homologous to or related to cellular proteins. J Virol. 1997;71(3):1963–74.PubMedGoogle Scholar
  38. 38.
    Moore PS, et al. Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science. 1996;274(5293):1739–44.PubMedCrossRefGoogle Scholar
  39. 39.
    Sun R, et al. A viral gene that activates lytic cycle expression of Kaposi’s sarcoma- associated herpesvirus. Proc Natl Acad Sci USA. 1998;95(18):10866–71.PubMedCrossRefGoogle Scholar
  40. 40.
    Lukac DM, et al. Reactivation of Kaposi’s sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein. Virology. 1998;252(2):304–12.PubMedCrossRefGoogle Scholar
  41. 41.
    Wu TT, et al. Rta of murine gammaherpesvirus 68 reactivates the complete lytic cycle from latency. J Virol. 2000;74(8):3659–67.PubMedCrossRefGoogle Scholar
  42. 42.
    Ragoczy T, Heston L, Miller G. The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes. J Virol. 1998;72(10):7978–84.PubMedGoogle Scholar
  43. 43.
    Countryman J, Miller G. Activation of expression of latent Epstein-Barr herpesvirus after gene transfer with a small cloned subfragment of heterogeneous viral DNA. Proc Natl Acad Sci USA. 1985;82(12):4085–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Zalani S, Holley-Guthrie E, Kenney S. Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism. Proc Natl Acad Sci USA. 1996;93(17):9194–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Johannsen E, et al. Proteins of purified Epstein-Barr virus. Proc Natl Acad Sci USA. 2004;101(46):16286–91.PubMedCrossRefGoogle Scholar
  46. 46.
    Zhu FX, et al. Virion proteins of Kaposi’s sarcoma-associated herpesvirus. J Virol. 2005;79(2):800–11.PubMedCrossRefGoogle Scholar
  47. 47.
    Tanner J, et al. Epstein-Barr virus gp350/220 binding to the B lymphocyte C3d receptor mediates adsorption, capping, and endocytosis. Cell. 1987;50(2):203–13.PubMedCrossRefGoogle Scholar
  48. 48.
    Nemerow GR, et al. Identification of gp350 as the viral glycoprotein mediating attachment of Epstein-Barr virus (EBV) to the EBV/C3d receptor of B cells: sequence homology of gp350 and C3 complement fragment C3d. J Virol. 1987;61(5):1416–20.PubMedGoogle Scholar
  49. 49.
    Thorley-Lawson DA, Geilinger K. Monoclonal antibodies against the major glycoprotein (gp350/220) of Epstein-Barr virus neutralize infectivity. Proc Natl Acad Sci USA. 1980;77(9):5307–11.PubMedCrossRefGoogle Scholar
  50. 50.
    Hutt-Fletcher LM. Epstein-Barr virus entry. J Virol. 2007;81(15):7825–32.PubMedCrossRefGoogle Scholar
  51. 51.
    Sixbey JW, Yao QY. Immunoglobulin A-induced shift of Epstein-Barr virus tissue tropism. Science. 1992;255(5051):1578–80.PubMedCrossRefGoogle Scholar
  52. 52.
    Turk SM, et al. Antibodies to gp350/220 enhance the ability of Epstein-Barr virus to infect epithelial cells. J Virol. 2006;80(19):9628–33.PubMedCrossRefGoogle Scholar
  53. 53.
    Gillet L, Stevenson PG. Evidence for a multiprotein gamma-2 herpesvirus entry complex. J Virol. 2007;81(23):13082–91.PubMedCrossRefGoogle Scholar
  54. 54.
    Leight ER, Sugden B. EBNA-1: a protein pivotal to latent infection by Epstein-Barr virus. Rev Med Virol. 2000;10(2):83–100.PubMedCrossRefGoogle Scholar
  55. 55.
    Barbera AJ, et al. Kaposi’s sarcoma-associated herpesvirus LANA hitches a ride on the chromosome. Cell Cycle. 2006;5(10):1048–52.PubMedGoogle Scholar
  56. 56.
    Lee MA, Diamond ME, Yates JL. Genetic evidence that EBNA-1 is needed for efficient, stable latent infection by Epstein-Barr virus. J Virol. 1999;73(4):2974–82.PubMedGoogle Scholar
  57. 57.
    Ye FC, et al. Disruption of Kaposi’s sarcoma-associated herpesvirus latent nuclear antigen leads to abortive episome persistence. J Virol. 2004;78(20):11121–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Fowler P, et al. ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency. J Gen Virol. 2003;84(Pt 12):3405–16.PubMedCrossRefGoogle Scholar
  59. 59.
    Moorman NJ, Virgin HWt, Speck SH. Disruption of the gene encoding the gammaHV68 v-GPCR leads to decreased efficiency of reactivation from latency. Virology. 2003;307(2):179–90.PubMedCrossRefGoogle Scholar
  60. 60.
    Wilson JB, Bell JL, Levine AJ. Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice. EMBO J. 1996;15(12):3117–26.PubMedGoogle Scholar
  61. 61.
    Fakhari FD, et al. The latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus induces B cell hyperplasia and lymphoma. J Clin Invest. 2006;116(3):735–42.PubMedCrossRefGoogle Scholar
  62. 62.
    Gires O, et al. Latent membrane protein 1 of Epstein-Barr virus mimics a constitutively active receptor molecule. EMBO J. 1997;16(20):6131–40.PubMedCrossRefGoogle Scholar
  63. 63.
    Miller CL, et al. Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases. Immunity. 1995;2(2):155–66.PubMedCrossRefGoogle Scholar
  64. 64.
    Wang D, Liebowitz D, Kieff E. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell. 1985;43(3 Pt 2):831–40.PubMedCrossRefGoogle Scholar
  65. 65.
    Thorley-Lawson DA. Epstein-Barr virus: exploiting the immune system. Nat Rev Immunol. 2001;1(1):75–82.PubMedCrossRefGoogle Scholar
  66. 66.
    Dittmer D, et al. A cluster of latently expressed genes in Kaposi’s sarcoma-associated herpesvirus. J Virol. 1998;72(10):8309–15.PubMedGoogle Scholar
  67. 67.
    Sarid R, et al. Transcription mapping of the Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) genome in a body cavity-based lymphoma cell line (BC-1). J Virol. 1998;72(2):1005–12.PubMedGoogle Scholar
  68. 68.
    Sun Q, Zachariah S, Chaudhary PM. The human herpes virus 8-encoded viral FLICE-inhibitory protein induces cellular transformation via NF-kappaB activation. J Biol Chem. 2003;278(52):52437–45.PubMedCrossRefGoogle Scholar
  69. 69.
    Verschuren EW, et al. The role of p53 in suppression of KSHV cyclin-induced lymphomagenesis. Cancer Res. 2004;64(2):581–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Staskus KA, et al. Kaposi’s sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol. 1997;71(1):715–9.PubMedGoogle Scholar
  71. 71.
    Zhong W, et al. Restricted expression of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma. Proc Natl Acad Sci USA. 1996;93(13):6641–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Sadler R, et al. A complex translational program generates multiple novel proteins from the latently expressed kaposin (K12) locus of Kaposi’s sarcoma-associated herpesvirus. J Virol. 1999;73(7):5722–30.PubMedGoogle Scholar
  73. 73.
    Muralidhar S, et al. Identification of kaposin (open reading frame K12) as a human herpesvirus 8 (Kaposi’s sarcoma-associated herpesvirus) transforming gene. J Virol. 1998;72(6):4980–8.PubMedGoogle Scholar
  74. 74.
    Husain SM, et al. Murine gammaherpesvirus M2 gene is latency-associated and its protein a target for CD8(+) T lymphocytes. Proc Natl Acad Sci USA. 1999;96(13):7508–13.PubMedCrossRefGoogle Scholar
  75. 75.
    Rochford R, et al. Kinetics of murine gammaherpesvirus 68 gene expression following infection of murine cells in culture and in mice. J Virol. 2001;75(11):4955–63.PubMedCrossRefGoogle Scholar
  76. 76.
    Marques S, et al. Selective gene expression of latent murine gammaherpesvirus 68 in B lymphocytes. J Virol. 2003;77(13):7308–18.PubMedCrossRefGoogle Scholar
  77. 77.
    Martinez-Guzman D, et al. Transcription program of murine gammaherpesvirus 68. J Virol. 2003;77(19):10488–503.PubMedCrossRefGoogle Scholar
  78. 78.
    Virgin HWt, et al. Three distinct regions of the murine gammaherpesvirus 68 genome are transcriptionally active in latently infected mice. J Virol. 1999;73(3):2321–32.PubMedGoogle Scholar
  79. 79.
    Bowden RJ, et al. Murine gammaherpesvirus 68 encodes tRNA-like sequences which are expressed during latency. J Gen Virol. 1997;78(Pt 7):1675–87.PubMedGoogle Scholar
  80. 80.
    Flano E, et al. Latent murine gamma-herpesvirus infection is established in activated B cells, dendritic cells, and macrophages. J Immunol. 2000;165(2):1074–81.PubMedGoogle Scholar
  81. 81.
    Stewart JP, et al. Lung epithelial cells are a major site of murine gammaherpesvirus persistence. J Exp Med. 1998;187(12):1941–51.PubMedCrossRefGoogle Scholar
  82. 82.
    Weck KE, et al. Macrophages are the major reservoir of latent murine gammaherpesvirus 68 in peritoneal cells. J Virol. 1999;73(4):3273–83.PubMedGoogle Scholar
  83. 83.
    van Dyk LF, Virgin HWt, Speck SH. Maintenance of gammaherpesvirus latency requires viral cyclin in the absence of B lymphocytes. J Virol. 2003;77(9):5118–26.PubMedCrossRefGoogle Scholar
  84. 84.
    de Lima BD, et al. Murine gammaherpesvirus 68 bcl-2 homologue contributes to latency establishment in vivo. J Gen Virol. 2005;86(Pt 1):31–40.PubMedCrossRefGoogle Scholar
  85. 85.
    Moorman NJ, Willer DO, Speck SH. The gammaherpesvirus 68 latency-associated nuclear antigen homolog is critical for the establishment of splenic latency. J Virol. 2003;77(19):10295–303.PubMedCrossRefGoogle Scholar
  86. 86.
    Macrae AI, et al. Murid herpesvirus 4 strain 68 M2 protein is a B-cell-associated antigen important for latency but not lymphocytosis. J Virol. 2003;77(17):9700–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Stevenson PG, et al. K3-mediated evasion of CD8(+) T cells aids amplification of a latent gamma-herpesvirus. Nat Immunol. 2002;3(8):733–40.PubMedGoogle Scholar
  88. 88.
    Jacoby MA, Virgin HWt, Speck SH. Disruption of the M2 gene of murine gammaherpesvirus 68 alters splenic latency following intranasal, but not intraperitoneal, inoculation. J Virol. 2002;76(4):1790–801.PubMedCrossRefGoogle Scholar
  89. 89.
    Loh J, et al. A surface groove essential for viral Bcl-2 function during chronic infection in vivo. PLoS Pathog. 2005;1(1):e10.PubMedCrossRefGoogle Scholar
  90. 90.
    Fruh K, et al. Immune evasion by a novel family of viral PHD/LAP-finger proteins of gamma-2 herpesviruses and poxviruses. Virus Res. 2002;88(1–2):55–69.PubMedCrossRefGoogle Scholar
  91. 91.
    Madureira PA, et al. Murine gamma-herpesvirus 68 latency protein M2 binds to Vav signaling proteins and inhibits B-cell receptor-induced cell cycle arrest and apoptosis in WEHI-231 B cells. J Biol Chem. 2005;280(45):37310–8.PubMedCrossRefGoogle Scholar
  92. 92.
    Rodrigues L, et al. Activation of Vav by the gammaherpesvirus M2 protein contributes to the establishment of viral latency in B lymphocytes. J Virol. 2006;80(12):6123–35.PubMedCrossRefGoogle Scholar
  93. 93.
    Siegel AM, Herskowitz JH, Speck SH. The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation. PLoS Pathog. 2008;4(4):e1000039.PubMedCrossRefGoogle Scholar
  94. 94.
    Liang X, et al. Inhibition of interferon-mediated antiviral activity by murine gammaherpesvirus 68 latency-associated M2 protein. J Virol. 2004;78(22):12416–27.PubMedCrossRefGoogle Scholar
  95. 95.
    Liang X, et al. Deregulation of DNA damage signal transduction by herpesvirus latency-associated M2. J Virol. 2006;80(12):5862–74.PubMedCrossRefGoogle Scholar
  96. 96.
    Wang GH, Garvey TL, Cohen JI. The murine gammaherpesvirus-68 M11 protein inhibits Fas- and TNF-induced apoptosis. J Gen Virol. 1999;80(Pt 10):2737–40.PubMedGoogle Scholar
  97. 97.
    Ku B, et al. Structural and biochemical bases for the inhibition of autophagy and apoptosis by viral BCL-2 of murine gamma-herpesvirus 68. PLoS Pathog. 2008;4(2):e25.PubMedCrossRefGoogle Scholar
  98. 98.
    Feng P, et al. A novel inhibitory mechanism of mitochondrion-dependent apoptosis by a herpesviral protein. PLoS Pathog. 2007;3(12):e174.PubMedCrossRefGoogle Scholar
  99. 99.
    Miller CL, et al. An integral membrane protein (LMP2) blocks reactivation of Epstein-Barr virus from latency following surface immunoglobulin crosslinking. Proc Natl Acad Sci USA. 1994;91(2):772–6.PubMedCrossRefGoogle Scholar
  100. 100.
    Lan K, et al. Kaposi’s sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen inhibits lytic replication by targeting Rta: a potential mechanism for virus-mediated control of latency. J Virol. 2004;78(12):6585–94.PubMedCrossRefGoogle Scholar
  101. 101.
    Li Q, et al. Genetic disruption of KSHV major latent nuclear antigen LANA enhances viral lytic transcriptional program. Virology. 2008;379(2):234–44.PubMedCrossRefGoogle Scholar
  102. 102.
    Ye FC, et al. Kaposi’s sarcoma-associated herpesvirus latent gene vFLIP inhibits viral lytic replication through NF-kappaB-mediated suppression of the AP-1 pathway: a novel mechanism of virus control of latency. J Virol. 2008;82(9):4235–49.PubMedCrossRefGoogle Scholar
  103. 103.
    Pfeffer S, et al. Identification of virus-encoded microRNAs. Science. 2004;304(5671):734–6.PubMedCrossRefGoogle Scholar
  104. 104.
    Boss IW, Plaisance KB, Renne R. Role of virus-encoded microRNAs in herpesvirus biology. Trends Microbiol. 2009;17(12):544–53.PubMedCrossRefGoogle Scholar
  105. 105.
    Bellare P, Ganem D. Regulation of KSHV lytic switch protein expression by a virus-encoded microRNA: an evolutionary adaptation that fine-tunes lytic reactivation. Cell Host Microbe. 2009;6(6):570–5.PubMedCrossRefGoogle Scholar
  106. 106.
    Lu F et al. Epigenetic regulation of Kaposi’s sarcoma-associated herpesvirus latency by virus-encoded microRNAs that target Rta and the cellular Rbl2-DNMT pathway. J Virol. 84(6):2697–706.Google Scholar
  107. 107.
    Rooney CM, et al. Adoptive immunotherapy of EBV-associated malignancies with EBV-specific cytotoxic T-cell lines. Curr Top Microbiol Immunol. 2001;258:221–9.PubMedGoogle Scholar
  108. 108.
    Rooney CM et al. Immunotherapy for Epstein-Barr virus-associated cancers. J Natl Cancer Inst Monogr. 1998;(23):89–93.Google Scholar
  109. 109.
    Steven NM, et al. Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response. J Exp Med. 1997;185(9):1605–17.PubMedCrossRefGoogle Scholar
  110. 110.
    Pudney VA, et al. CD8+ immunodominance among Epstein-Barr virus lytic cycle antigens directly reflects the efficiency of antigen presentation in lytically infected cells. J Exp Med. 2005;201(3):349–60.PubMedCrossRefGoogle Scholar
  111. 111.
    Woodberry T, et al. Differential targeting and shifts in the immunodominance of Epstein-Barr virus—specific CD8 and CD4 T cell responses during acute and persistent infection. J Infect Dis. 2005;192(9):1513–24.PubMedCrossRefGoogle Scholar
  112. 112.
    Landais E, Saulquin X, Houssaint E. The human T cell immune response to Epstein-Barr virus. Int J Dev Biol. 2005;49(2–3):285–92.PubMedCrossRefGoogle Scholar
  113. 113.
    Steven NM, et al. Epitope focusing in the primary cytotoxic T cell response to Epstein-Barr virus and its relationship to T cell memory. J Exp Med. 1996;184(5):1801–13.PubMedCrossRefGoogle Scholar
  114. 114.
    Levitskaya J, et al. Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature. 1995;375(6533):685–8.PubMedCrossRefGoogle Scholar
  115. 115.
    Levitskaya J, et al. Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein-Barr virus nuclear antigen 1. Proc Natl Acad Sci USA. 1997;94(23):12616–21.PubMedCrossRefGoogle Scholar
  116. 116.
    Yin Y, Manoury B, Fahraeus R. Self-inhibition of synthesis and antigen presentation by Epstein-Barr virus-encoded EBNA1. Science. 2003;301(5638):1371–4.PubMedCrossRefGoogle Scholar
  117. 117.
    Schubert U, et al. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature. 2000;404(6779):770–4.PubMedCrossRefGoogle Scholar
  118. 118.
    Reits EA, et al. The major substrates for TAP in vivo are derived from newly synthesized proteins. Nature. 2000;404(6779):774–8.PubMedCrossRefGoogle Scholar
  119. 119.
    Lee SP, et al. CD8 T cell recognition of endogenously expressed Epstein-Barr virus nuclear antigen 1. J Exp Med. 2004;199(10):1409–20.PubMedCrossRefGoogle Scholar
  120. 120.
    Voo KS, et al. Evidence for the presentation of major histocompatibility complex class I-restricted Epstein-Barr virus nuclear antigen 1 peptides to CD8 + T lymphocytes. J Exp Med. 2004;199(4):459–70.PubMedCrossRefGoogle Scholar
  121. 121.
    Tellam J, et al. Endogenous presentation of CD8 + T cell epitopes from Epstein-Barr virus-encoded nuclear antigen 1. J Exp Med. 2004;199(10):1421–31.PubMedCrossRefGoogle Scholar
  122. 122.
    Saulquin X, et al. A global appraisal of immunodominant CD8 T cell responses to Epstein-Barr virus and cytomegalovirus by bulk screening. Eur J Immunol. 2000;30(9):2531–9.PubMedCrossRefGoogle Scholar
  123. 123.
    Tan LC, et al. A re-evaluation of the frequency of CD8 + T cells specific for EBV in healthy virus carriers. J Immunol. 1999;162(3):1827–35.PubMedGoogle Scholar
  124. 124.
    Murray RJ, et al. Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): implications for the immune control of EBV-positive malignancies. J Exp Med. 1992;176(1):157–68.PubMedCrossRefGoogle Scholar
  125. 125.
    Khanna R, et al. Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development. J Exp Med. 1992;176(1):169–76.PubMedCrossRefGoogle Scholar
  126. 126.
    Meij P, et al. Identification and prevalence of CD8(+) T-cell responses directed against Epstein-Barr virus-encoded latent membrane protein 1 and latent membrane protein 2. Int J Cancer. 2002;99(1):93–9.PubMedCrossRefGoogle Scholar
  127. 127.
    Wang QJ, et al. Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell response to viral lytic cycle proteins. Blood. 2001;97(8):2366–73.PubMedCrossRefGoogle Scholar
  128. 128.
    Lambert M, et al. Differences in the frequency and function of HHV8-specific CD8 T cells between asymptomatic HHV8 infection and Kaposi sarcoma. Blood. 2006;108(12):3871–80.PubMedCrossRefGoogle Scholar
  129. 129.
    Robey RC, et al. The CD8 and CD4 T-cell response against Kaposi’s sarcoma-associated herpesvirus is skewed towards early and late lytic antigens. PLoS One. 2009;4(6):e5890.PubMedCrossRefGoogle Scholar
  130. 130.
    Zaldumbide A, et al. In cis inhibition of antigen processing by the latency-associated nuclear antigen I of Kaposi sarcoma herpes virus. Mol Immunol. 2007;44(6):1352–60.PubMedCrossRefGoogle Scholar
  131. 131.
    Guihot A, et al. Low T cell responses to human herpesvirus 8 in patients with AIDS-related and classic Kaposi sarcoma. J Infect Dis. 2006;194(8):1078–88.PubMedCrossRefGoogle Scholar
  132. 132.
    Brander C, et al. Definition of an optimal cytotoxic T lymphocyte epitope in the latently expressed Kaposi’s sarcoma-associated herpesvirus kaposin protein. J Infect Dis. 2001;184(2):119–26.PubMedCrossRefGoogle Scholar
  133. 133.
    Freeman ML, et al. Two kinetic patterns of epitope-specific CD8 T-cell responses following murine gammaherpesvirus 68 infection. J Virol. 2010;84(6):2881–92.PubMedCrossRefGoogle Scholar
  134. 134.
    Gredmark-Russ S, et al. The CD8 T-cell response against murine gammaherpesvirus 68 is directed toward a broad repertoire of epitopes from both early and late antigens. J Virol. 2008;82(24):12205–12.PubMedCrossRefGoogle Scholar
  135. 135.
    Aichinger G, et al. Major histocompatibility complex class II-dependent unfolding, transport, and degradation of endogenous proteins. J Biol Chem. 1997;272(46):29127–36.PubMedCrossRefGoogle Scholar
  136. 136.
    Paludan C, et al. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science. 2005;307(5709):593–6.PubMedCrossRefGoogle Scholar
  137. 137.
    Brown DM. Cytolytic CD4 cells: direct mediators in infectious disease and malignancy. Cell Immunol. 2010;262(2):89–95.PubMedCrossRefGoogle Scholar
  138. 138.
    Nikiforow S, et al. Cytolytic CD4(+)-T-cell clones reactive to EBNA1 inhibit Epstein-Barr virus-induced B-cell proliferation. J Virol. 2003;77(22):12088–104.PubMedCrossRefGoogle Scholar
  139. 139.
    Long HM, et al. CD4 + T-cell responses to Epstein-Barr virus (EBV) latent-cycle antigens and the recognition of EBV-transformed lymphoblastoid cell lines. J Virol. 2005;79(8):4896–907.PubMedCrossRefGoogle Scholar
  140. 140.
    Paludan C, et al. Epstein-Barr nuclear antigen 1-specific CD4(+) Th1 cells kill Burkitt’s lymphoma cells. J Immunol. 2002;169(3):1593–603.PubMedGoogle Scholar
  141. 141.
    Landais E, et al. Direct killing of Epstein-Barr virus (EBV)-infected B cells by CD4 T cells directed against the EBV lytic protein BHRF1. Blood. 2004;103(4):1408–16.PubMedCrossRefGoogle Scholar
  142. 142.
    Omiya R, et al. Inhibition of EBV-induced lymphoproliferation by CD4(+) T cells specific for an MHC class II promiscuous epitope. J Immunol. 2002;169(4):2172–9.PubMedGoogle Scholar
  143. 143.
    Leen A, et al. Differential immunogenicity of Epstein-Barr virus latent-cycle proteins for human CD4(+) T-helper 1 responses. J Virol. 2001;75(18):8649–59.PubMedCrossRefGoogle Scholar
  144. 144.
    Munz C, et al. Human CD4(+) T lymphocytes consistently respond to the latent Epstein-Barr virus nuclear antigen EBNA1. J Exp Med. 2000;191(10):1649–60.PubMedCrossRefGoogle Scholar
  145. 145.
    Bickham K, et al. EBNA1-specific CD4 + T cells in healthy carriers of Epstein-Barr virus are primarily Th1 in function. J Clin Invest. 2001;107(1):121–30.PubMedCrossRefGoogle Scholar
  146. 146.
    Moormann AM, et al. Children with endemic Burkitt lymphoma are deficient in EBNA1-specific IFN-gamma T cell responses. Int J Cancer. 2009;124(7):1721–6.PubMedCrossRefGoogle Scholar
  147. 147.
    Heller KN, et al. Patients with Epstein Barr virus-positive lymphomas have decreased CD4(+) T-cell responses to the viral nuclear antigen 1. Int J Cancer. 2008;123(12):2824–31.PubMedCrossRefGoogle Scholar
  148. 148.
    Haigh TA, et al. EBV latent membrane proteins (LMPs) 1 and 2 as immunotherapeutic targets: LMP-specific CD4 + cytotoxic T cell recognition of EBV-transformed B cell lines. J Immunol. 2008;180(3):1643–54.PubMedGoogle Scholar
  149. 149.
    Adhikary D, et al. Control of Epstein-Barr virus infection in vitro by T helper cells specific for virion glycoproteins. J Exp Med. 2006;203(4):995–1006.PubMedCrossRefGoogle Scholar
  150. 150.
    Wallace LE, et al. Identification of two T-cell epitopes on the candidate Epstein-Barr virus vaccine glycoprotein gp340 recognized by CD4 + T-cell clones. J Virol. 1991;65(7):3821–8.PubMedGoogle Scholar
  151. 151.
    Christensen JP, Doherty PC. Quantitative analysis of the acute and long-term CD4(+) T-cell response to a persistent gammaherpesvirus. J Virol. 1999;73(5):4279–83.PubMedGoogle Scholar
  152. 152.
    Cardin RD, et al. Progressive loss of CD8 + T cell-mediated control of a gamma-herpesvirus in the absence of CD4 + T cells. J Exp Med. 1996;184(3):863–71.PubMedCrossRefGoogle Scholar
  153. 153.
    Christensen JP, et al. CD4(+) T cell-mediated control of a gamma-herpesvirus in B cell-deficient mice is mediated by IFN-gamma. Proc Natl Acad Sci USA. 1999;96(9):5135–40.PubMedCrossRefGoogle Scholar
  154. 154.
    Stuller KA, Flano E. CD4 T cells mediate killing during persistent gammaherpesvirus 68 infection. J Virol. 2009;83(9):4700–3.PubMedCrossRefGoogle Scholar
  155. 155.
    Stuller KA, Cush SS, Flano E. Persistent gamma-herpesvirus infection induces a CD4 T cell response containing functionally distinct effector populations. J Immunol. 2010;184(7):3850–6.PubMedCrossRefGoogle Scholar
  156. 156.
    Flano E, et al. Analysis of virus-specific CD4(+) t cells during long-term gammaherpesvirus infection. J Virol. 2001;75(16):7744–8.PubMedCrossRefGoogle Scholar
  157. 157.
    Thorley-Lawson DA, Poodry CA. Identification and isolation of the main component (gp350-gp220) of Epstein-Barr virus responsible for generating neutralizing antibodies in vivo. J Virol. 1982;43(2):730–6.PubMedGoogle Scholar
  158. 158.
    Yao QY, et al. Salivary and serum IgA antibodies to the Epstein-Barr virus glycoprotein gp340: incidence and potential for virus neutralization. Int J Cancer. 1991;48(1):45–50.PubMedCrossRefGoogle Scholar
  159. 159.
    Khanna R, Burrows SR, Moss DJ. Immune regulation in Epstein-Barr virus-associated diseases. Microbiol Rev. 1995;59(3):387–405.PubMedGoogle Scholar
  160. 160.
    Henle G, Henle W. Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma. Int J Cancer. 1976;17(1):1–7.PubMedCrossRefGoogle Scholar
  161. 161.
    Kimball LE, et al. Reduced levels of neutralizing antibodies to Kaposi sarcoma-associated herpesvirus in persons with a history of Kaposi sarcoma. J Infect Dis. 2004;189(11):2016–22.PubMedCrossRefGoogle Scholar
  162. 162.
    Stevenson PG, Doherty PC. Kinetic analysis of the specific host response to a murine gammaherpesvirus. J Virol. 1998;72(2):943–9.PubMedGoogle Scholar
  163. 163.
    Doherty PC, et al. Dissecting the host response to a gamma-herpesvirus. Philos Trans R Soc Lond B Biol Sci. 2001;356(1408):581–93.PubMedCrossRefGoogle Scholar
  164. 164.
    Kim IJ, et al. Antibody-mediated control of persistent gamma-herpesvirus infection. J Immunol. 2002;168(8):3958–64.PubMedGoogle Scholar
  165. 165.
    Stevenson PG, et al. Immunological control of a murine gammaherpesvirus independent of CD8 + T cells. J Gen Virol. 1999;80(Pt 2):477–83.PubMedGoogle Scholar
  166. 166.
    Tibbetts SA, et al. Effective vaccination against long-term gammaherpesvirus latency. J Virol. 2003;77(4):2522–9.PubMedCrossRefGoogle Scholar
  167. 167.
    Bennett NJ, May JS, Stevenson PG. Gamma-herpesvirus latency requires T cell evasion during episome maintenance. PLoS Biol. 2005;3(4):e120.PubMedCrossRefGoogle Scholar
  168. 168.
    Ressing ME, et al. Epstein-Barr virus evasion of CD8(+) and CD4(+) T cell immunity via concerted actions of multiple gene products. Semin Cancer Biol. 2008;18(6):397–408.PubMedCrossRefGoogle Scholar
  169. 169.
    Liang C, Lee JS, Jung JU. Immune evasion in Kaposi’s sarcoma-associated herpes virus associated oncogenesis. Semin Cancer Biol. 2008;18(6):423–36.PubMedCrossRefGoogle Scholar
  170. 170.
    Coscoy L. Immune evasion by Kaposi’s sarcoma-associated herpesvirus. Nat Rev Immunol. 2007;7(5):391–401.PubMedCrossRefGoogle Scholar
  171. 171.
    Rezaee SA, et al. Kaposi’s sarcoma-associated herpesvirus immune modulation: an overview. J Gen Virol. 2006;87(Pt 7):1781–804.PubMedCrossRefGoogle Scholar
  172. 172.
    Areste C, Blackbourn DJ. Modulation of the immune system by Kaposi’s sarcoma-associated herpesvirus. Trends Microbiol. 2009;17(3):119–29.PubMedCrossRefGoogle Scholar
  173. 173.
    Stevenson PG. Immune evasion by gamma-herpesviruses. Curr Opin Immunol. 2004;16(4):456–62.PubMedCrossRefGoogle Scholar
  174. 174.
    Zuo J, et al. The DNase of gammaherpesviruses impairs recognition by virus-specific CD8 + T cells through an additional host shutoff function. J Virol. 2008;82(5):2385–93.PubMedCrossRefGoogle Scholar
  175. 175.
    Rowe M, et al. Host shutoff during productive Epstein-Barr virus infection is mediated by BGLF5 and may contribute to immune evasion. Proc Natl Acad Sci USA. 2007;104(9):3366–71.PubMedCrossRefGoogle Scholar
  176. 176.
    Liang C, E X, Jung JU. Downregulation of autophagy by herpesvirus Bcl-2 homologs. Autophagy. 2008;4(3):268–72.PubMedGoogle Scholar
  177. 177.
    Pattingre S, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005;122(6):927–39.PubMedCrossRefGoogle Scholar
  178. 178.
    Dengjel J, et al. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci USA. 2005;102(22):7922–7.PubMedCrossRefGoogle Scholar
  179. 179.
    Moore KW, et al. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990;248(4960):1230–4.PubMedCrossRefGoogle Scholar
  180. 180.
    Bridgeman A, et al. A secreted chemokine binding protein encoded by murine gammaherpesvirus-68 is necessary for the establishment of a normal latent load. J Exp Med. 2001;194(3):301–12.PubMedCrossRefGoogle Scholar
  181. 181.
    Kledal TN, et al. A broad-spectrum chemokine antagonist encoded by Kaposi’s sarcoma-associated herpesvirus. Science. 1997;277(5332):1656–9.PubMedCrossRefGoogle Scholar
  182. 182.
    Sozzani S, et al. The viral chemokine macrophage inflammatory protein-II is a selective Th2 chemoattractant. Blood. 1998;92(11):4036–9.PubMedGoogle Scholar
  183. 183.
    Stine JT, et al. KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates angiogenesis, and selectively chemoattracts TH2 cells. Blood. 2000;95(4):1151–7.PubMedGoogle Scholar
  184. 184.
    Moore KW, et al. Interleukin-10. Annu Rev Immunol. 1993;11:165–90.PubMedCrossRefGoogle Scholar
  185. 185.
    Nachmani D, et al. Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. Cell Host Microbe. 2009;5(4):376–85.PubMedCrossRefGoogle Scholar
  186. 186.
    Levin MJ, et al. Immune response of elderly individuals to a live attenuated varicella vaccine. J Infect Dis. 1992;166(2):253–9.PubMedGoogle Scholar
  187. 187.
    Oxman MN, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271–84.PubMedCrossRefGoogle Scholar
  188. 188.
    Hoffman GJ, Lazarowitz SG, Hayward SD. Monoclonal antibody against a 250,000-dalton glycoprotein of Epstein-Barr virus identifies a membrane antigen and a neutralizing antigen. Proc Natl Acad Sci USA. 1980;77(5):2979–83.PubMedCrossRefGoogle Scholar
  189. 189.
    Epstein MA, et al. Protection of cottontop tamarins against Epstein-Barr virus-induced malignant lymphoma by a prototype subunit vaccine. Nature. 1985;318(6043):287–9.PubMedCrossRefGoogle Scholar
  190. 190.
    Morgan AJ, et al. Recombinant vaccinia virus expressing Epstein-Barr virus glycoprotein gp340 protects cottontop tamarins against EB virus-induced malignant lymphomas. J Med Virol. 1988;25(2):189–95.PubMedCrossRefGoogle Scholar
  191. 191.
    Ragot T, et al. Replication-defective recombinant adenovirus expressing the Epstein-Barr virus (EBV) envelope glycoprotein gp340/220 induces protective immunity against EBV-induced lymphomas in the cottontop tamarin. J Gen Virol. 1993;74(Pt 3):501–7.PubMedCrossRefGoogle Scholar
  192. 192.
    Gu SY, et al. First EBV vaccine trial in humans using recombinant vaccinia virus expressing the major membrane antigen. Dev Biol Stand. 1995;84:171–7.PubMedGoogle Scholar
  193. 193.
    Chang H, et al. Non-human primate model of Kaposi’s sarcoma-associated herpesvirus infection. PLoS Pathog. 2009;5(10):e1000606.PubMedCrossRefGoogle Scholar
  194. 194.
    Mansfield KG, et al. Experimental infection of rhesus and pig-tailed macaques with macaque rhadinoviruses. J Virol. 1999;73(12):10320–8.PubMedGoogle Scholar
  195. 195.
    Moghaddam A, et al. An animal model for acute and persistent Epstein-Barr virus infection. Science. 1997;276(5321):2030–3.PubMedCrossRefGoogle Scholar
  196. 196.
    Dittmer D, et al. Experimental transmission of Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) to SCID-hu Thy/Liv mice. J Exp Med. 1999;190(12):1857–68.PubMedCrossRefGoogle Scholar
  197. 197.
    Islas-Ohlmayer M, et al. Experimental infection of NOD/SCID mice reconstituted with human CD34 + cells with Epstein-Barr virus. J Virol. 2004;78(24):13891–900.PubMedCrossRefGoogle Scholar
  198. 198.
    Yajima M, et al. A new humanized mouse model of Epstein-Barr virus infection that reproduces persistent infection, lymphoproliferative disorder, and cell-mediated and humoral immune responses. J Infect Dis. 2008;198(5):673–82.PubMedCrossRefGoogle Scholar
  199. 199.
    Melkus MW, et al. Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nat Med. 2006;12(11):1316–22.PubMedCrossRefGoogle Scholar
  200. 200.
    Yajima M, et al. T cell-mediated control of Epstein-Barr virus infection in humanized mice. J Infect Dis. 2009;200(10):1611–5.PubMedCrossRefGoogle Scholar
  201. 201.
    Traggiai E, et al. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science. 2004;304(5667):104–7.PubMedCrossRefGoogle Scholar
  202. 202.
    Obar JJ, et al. T-cell responses to the M3 immune evasion protein of murid gammaherpesvirus 68 are partially protective and induced with lytic antigen kinetics. J Virol. 2004;78(19):10829–32.PubMedCrossRefGoogle Scholar
  203. 203.
    Woodland DL, et al. Vaccination against murine gamma-herpesvirus infection. Viral Immunol. 2001;14(3):217–26.PubMedCrossRefGoogle Scholar
  204. 204.
    Usherwood EJ, et al. Latent antigen vaccination in a model gammaherpesvirus infection. J Virol. 2001;75(17):8283–8.PubMedCrossRefGoogle Scholar
  205. 205.
    Stewart JP, et al. Murine gamma-herpesvirus 68 glycoprotein 150 protects against virus- induced mononucleosis: a model system for gamma-herpesvirus vaccination. Vaccine. 1999;17(2):152–7.PubMedCrossRefGoogle Scholar
  206. 206.
    Stevenson PG, et al. A gamma-herpesvirus sneaks through a CD8(+) T cell response primed to a lytic-phase epitope. Proc Natl Acad Sci USA. 1999;96(16):9281–6.PubMedCrossRefGoogle Scholar
  207. 207.
    Liu L, et al. T-cell vaccination alters the course of murine herpesvirus 68 infection and the establishment of viral latency in mice. J Virol. 1999;73(12):9849–57.PubMedGoogle Scholar
  208. 208.
    Stewart JP, et al. In vivo function of a gammaherpesvirus virion glycoprotein: influence on B-cell infection and mononucleosis. J Virol. 2004;78(19):10449–59.PubMedCrossRefGoogle Scholar
  209. 209.
    Arico E, et al. 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. 2004;22(11–12):1433–40.PubMedCrossRefGoogle Scholar
  210. 210.
    Fowler P, Efstathiou S. Vaccine potential of a murine gammaherpesvirus-68 mutant deficient for ORF73. J Gen Virol. 2004;85(Pt 3):609–13.PubMedCrossRefGoogle Scholar
  211. 211.
    Rickabaugh TM, et al. Generation of a latency-deficient gammaherpesvirus that is protective against secondary infection. J Virol. 2004;78(17):9215–23.PubMedCrossRefGoogle Scholar
  212. 212.
    Boname JM, et al. Protection against wild-type murine gammaherpesvirus-68 latency by a latency-deficient mutant. J Gen Virol. 2004;85(Pt 1):131–5.PubMedCrossRefGoogle Scholar
  213. 213.
    Jia Q et al. Induction of protective immunity against murine gammaherpesvirus-68 infection in the absence of viral latency. J Virol. 2009.Google Scholar
  214. 214.
    May JS, et al. Forced lytic replication impairs host colonization by a latency-deficient mutant of murine gammaherpesvirus-68. J Gen Virol. 2004;85(Pt 1):137–46.PubMedCrossRefGoogle Scholar
  215. 215.
    Zuo J, et al. The Epstein-Barr virus G-protein-coupled receptor contributes to immune evasion by targeting MHC class I molecules for degradation. PLoS Pathog. 2009;5(1):e1000255.PubMedCrossRefGoogle Scholar
  216. 216.
    Hislop AD, et al. A CD8 + T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates. J Exp Med. 2007;204(8):1863–73.PubMedCrossRefGoogle Scholar
  217. 217.
    Wang JT, et al. Epstein-Barr virus BGLF4 kinase suppresses the interferon regulatory factor 3 signaling pathway. J Virol. 2009;83(4):1856–69.PubMedCrossRefGoogle Scholar
  218. 218.
    Bentz GL, et al. Epstein-Barr virus BRLF1 inhibits transcription of IRF3 and IRF7 and suppresses induction of interferon-beta. Virology. 2010;402(1):121–8.PubMedCrossRefGoogle Scholar
  219. 219.
    Wu L, et al. Epstein-Barr virus LF2: an antagonist to type I interferon. J Virol. 2009;83(2):1140–6.PubMedCrossRefGoogle Scholar
  220. 220.
    Ishido S, et al. Downregulation of major histocompatibility complex class I molecules by Kaposi’s sarcoma-associated herpesvirus K3 and K5 proteins. J Virol. 2000;74(11):5300–9.PubMedCrossRefGoogle Scholar
  221. 221.
    Coscoy L, Ganem D. Kaposi’s sarcoma-associated herpesvirus encodes two proteins that block cell surface display of MHC class I chains by enhancing their endocytosis. Proc Natl Acad Sci USA. 2000;97(14):8051–6.PubMedCrossRefGoogle Scholar
  222. 222.
    Hwang S, et al. Conserved herpesviral kinase promotes viral persistence by inhibiting the IRF-3-mediated type I interferon response. Cell Host Microbe. 2009;5(2):166–78.PubMedCrossRefGoogle Scholar
  223. 223.
    Yu Y, Wang SE, Hayward GS. The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation. Immunity. 2005;22(1):59–70.PubMedCrossRefGoogle Scholar
  224. 224.
    Zhu FX, et al. 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. 2002;99(8):5573–8.PubMedCrossRefGoogle Scholar
  225. 225.
    Areste C, Mutocheluh M, Blackbourn DJ. Identification of caspase-mediated decay of interferon regulatory factor-3, exploited by a Kaposi sarcoma-associated herpesvirus immunoregulatory protein. J Biol Chem. 2009;284(35):23272–85.PubMedCrossRefGoogle Scholar
  226. 226.
    Wies E, et al. The Kaposi’s Sarcoma-associated Herpesvirus-encoded vIRF-3 inhibits cellular IRF-5. J Biol Chem. 2009;284(13):8525–38.PubMedCrossRefGoogle Scholar
  227. 227.
    Fuld S, et al. Inhibition of interferon signaling by the Kaposi’s sarcoma-associated herpesvirus full-length viral interferon regulatory factor 2 protein. J Virol. 2006;80(6):3092–7.PubMedCrossRefGoogle Scholar
  228. 228.
    Lin R, et al. HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators. Oncogene. 2001;20(7):800–11.PubMedCrossRefGoogle Scholar
  229. 229.
    Burysek L, et al. Functional analysis of human herpesvirus 8-encoded viral interferon regulatory factor 1 and its association with cellular interferon regulatory factors and p300. J Virol. 1999;73(9):7334–42.PubMedGoogle Scholar
  230. 230.
    Burysek L, Yeow WS, Pitha PM. Unique properties of a second human herpesvirus 8-encoded interferon regulatory factor (vIRF-2). J Hum Virol. 1999;2(1):19–32.PubMedGoogle Scholar
  231. 231.
    Bisson SA, Page AL, Ganem D. A Kaposi’s sarcoma-associated herpesvirus protein that forms inhibitory complexes with type I interferon receptor subunits, Jak and STAT proteins, and blocks interferon-mediated signal transduction. J Virol. 2009;83(10):5056–66.PubMedCrossRefGoogle Scholar
  232. 232.
    Boname JM, et al. Viral degradation of the MHC class I peptide loading complex. Immunity. 2004;20(3):305–17.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Molecular and Medical Pharmacology, School of MedicineUniversity of California at Los AngelesLos AngelesUSA
  2. 2.Oral Biology, School of DentistryUniversity of California at Los AngelesLos AngelesUSA
  3. 3.The Trudeau InstituteSaranac LakeUSA

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