Advertisement

Nonhuman Primate Gamma-herpesviruses and Their Role in Cancer

  • Ryan D. Estep
  • Scott W. Wong
Chapter
Part of the Current Cancer Research book series (CUCR)

Abstract

This chapter describes the nonhuman primate gamma-herpesviruses that have been isolated and found to induce oncogenesis in animals after experimental inoculation. These simian herpesviruses and animal models are important not only to understanding of the viral factors necessary for oncogenesis but also to the identification of host factors required for the viruses to induce disease. Three simian gamma-herpesviruses have been shown to be associated with oncogenesis, and a fourth is being further characterized. The first is Herpesvirus saimiri, the prototypic gamma-herpesvirus, which was found to induce lymphomas in New-World monkeys in 1970. The second is rhesus lymphocryptovirus, the rhesus macaque homologue of Epstein–Barr virus, which was also found to be associated with lymphoma in simian immunodeficiency virus (SIV)-infected animals. The third is rhesus macaque rhadinovirus, a close relative to human Kaposi’s sarcoma-associated herpesvirus, which has also been found to induce tumors, lymphoma, and mesenchymal cell proliferative lesion in SIV-infected animals. Each virus is described in detail, and strengths for tumor models are discussed.

Keywords

Rhesus Macaque Simian Immunodeficiency Virus Primary Effusion Lymphoma Herpesvirus Saimiri Viral Oncogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Albrecht JC, Nicholas J, Biller D, Cameron KR, Biesinger B, Newman C, Wittmann S, Craxton MA, Coleman H, Fleckenstein B et al (1992) Primary structure of the herpesvirus saimiri genome. J Virol 66:5047–5058PubMedGoogle Scholar
  2. Arvanitakis L, Geras-Raaka E, Varma A, Gershengorn MC, Cesarman E (1997) Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation. Nature 385:347–350PubMedCrossRefGoogle Scholar
  3. Bais C, Santomasso B, Coso O, Arvanitakis L, Raaka EG, Gutkind JS, Asch AS, Cesarman E, Gershengorn MC, Mesri EA, Gerhengorn MC (1998) G-protein-coupled receptor of Kaposi’s sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator. Nature 391:86–89PubMedCrossRefGoogle Scholar
  4. Baskin GB, Roberts ED, Kuebler D, Martin LN, Blauw B, Heeney J, Zurcher C (1995) Squamous epithelial proliferative lesions associated with rhesus Epstein–Barr virus in simian immunodeficiency virus-infected rhesus monkeys. J Infect Dis 172:535–539PubMedCrossRefGoogle Scholar
  5. Bergquam EP, Avery N, Shiigi SM, Axthelm MK, Wong SW (1999) Rhesus rhadinovirus establishes a latent infection in B lymphocytes in vivo. J Virol 73:7874–7876PubMedGoogle Scholar
  6. Biesinger B, Tsygankov AY, Fickenscher H, Emmrich F, Fleckenstein B, Bolen JB, Broker BM (1995) The product of the Herpesvirus saimiri open reading frame 1 (tip) interacts with T cell-specific kinase p56lck in transformed cells. J Biol Chem 270:4729–4734PubMedCrossRefGoogle Scholar
  7. Blaschke S, Hannig H, Buske C, Kaup FJ, Hunsmann G, Bodemer W (2001) Expression of the simian Epstein–Barr virus-encoded latent membrane protein-1 in malignant lymphomas of SIV-infected rhesus macaques. J Med Virol 65:114–120PubMedCrossRefGoogle Scholar
  8. Cai X, Schafer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, Raab-Traub N, Cullen BR (2006) Epstein–Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog 2:e23PubMedCrossRefGoogle Scholar
  9. Cannon M (2007) The KSHV and other human herpesviral G protein-coupled receptors. Curr Top Microbiol Immunol 312:137–156PubMedCrossRefGoogle Scholar
  10. Carville A, Mansfield KG (2008) Comparative pathobiology of macaque lymphocryptoviruses. Comp Med 58:57–67PubMedGoogle Scholar
  11. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM (1995) Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 332:1186–1191PubMedCrossRefGoogle Scholar
  12. Cesarman E, Nador RG, Bai F, Bohenzky RA, Russo JJ, Moore PS, Chang Y, Knowles DM (1996) Kaposi’s sarcoma-associated herpesvirus contains G protein-coupled receptor and cyclin D homologs which are expressed in Kaposi’s sarcoma and malignant lymphoma. J Virol 70:8218–8223PubMedGoogle Scholar
  13. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266:1865–1869PubMedCrossRefGoogle Scholar
  14. Cho YG, Gordadze AV, Ling PD, Wang F (1999) Evolution of two types of rhesus lymphocryptovirus similar to type 1 and type 2 Epstein–Barr virus. J Virol 73:9206–9212PubMedGoogle Scholar
  15. Choi JK, Ishido S, Jung JU (2000) The collagen repeat sequence is a determinant of the degree of herpesvirus saimiri STP transforming activity. J Virol 74:8102–8110PubMedCrossRefGoogle Scholar
  16. Damania B, Li M, Choi JK, Alexander L, Jung JU, Desrosiers RC (1999) Identification of the R1 oncogene and its protein product from the rhadinovirus of rhesus monkeys. J Virol 73:5123–5131PubMedGoogle Scholar
  17. Damania B, DeMaria M, Jung JU, Desrosiers RC (2000) Activation of lymphocyte signaling by the R1 protein of rhesus monkey rhadinovirus. J Virol 74:2721–2730PubMedCrossRefGoogle Scholar
  18. Damania B, Desrosiers RC (2001) Simian homologues of human herpesvirus 8. Philos Trans R Soc Lond B Biol Sci 356:535–543PubMedCrossRefGoogle Scholar
  19. Desrosiers RC, Falk LA (1982) Herpesvirus saimiri strain variability. J Virol 43:352–356PubMedGoogle Scholar
  20. Duboise SM, Guo J, Czajak S, Desrosiers RC, Jung JU (1998) STP and Tip are essential for herpesvirus saimiri oncogenicity. J Virol 72:1308–1313PubMedGoogle Scholar
  21. Dunkel VC, Pry TW, Henle G, Henle W (1972) Immunofluorescence tests for antibodies to Epstein–Barr virus with sera of lower primates. J Natl Cancer Inst 49:435–440PubMedGoogle Scholar
  22. Dykxhoorn DM (2007) MicroRNAs in viral replication and pathogenesis. DNA Cell Biol 26:239–249PubMedCrossRefGoogle Scholar
  23. Ensser A, Thurau M, Wittmann S, Fickenscher H (2003) The genome of herpesvirus saimiri C488 which is capable of transforming human T cells. Virology 314:471–487PubMedCrossRefGoogle Scholar
  24. Estep RD, Axthelm MK, Wong SW (2003) A G protein-coupled receptor encoded by rhesus rhadinovirus is similar to ORF74 of Kaposi’s sarcoma-associated herpesvirus. J Virol 77:1738–1746PubMedCrossRefGoogle Scholar
  25. Estep RD, Powers MF, Yen BK, Li H, Wong SW (2007) Construction of an infectious rhesus rhadinovirus bacterial artificial chromosome for the analysis of Kaposi’s sarcoma-associated herpesvirus-related disease development. J Virol 81:2957–2969PubMedCrossRefGoogle Scholar
  26. Farrell PJ (1995) Epstein–Barr virus immortalizing genes. Trends Microbiol 3:105–109PubMedCrossRefGoogle Scholar
  27. Fickenscher H, Fleckenstein B (2001) Herpesvirus saimiri. Philos Trans R Soc Lond B Biol Sci 356:545–567PubMedCrossRefGoogle Scholar
  28. Fields BN, Knipe DM, Howley PM, Griffin DE (2007) Fields’ virology, 5th edn. Wolters Kluwer Health/Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  29. Gao SJ, Boshoff C, Jayachandra S, Weiss RA, Chang Y, Moore PS (1997) KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway. Oncogene 15:1979–1985PubMedCrossRefGoogle Scholar
  30. Gottwein E, Cullen BR (2008) Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe 3:375–387PubMedCrossRefGoogle Scholar
  31. Greensill J, Sheldon JA, Renwick NM, Beer BE, Norley S, Goudsmit J, Schulz TF (2000) Two distinct gamma-2 herpesviruses in African green monkeys: a second gamma-2 herpesvirus lineage among old world primates? J Virol 74:1572–1577PubMedCrossRefGoogle Scholar
  32. Habis A, Baskin GB, Murphey-Corb M, Levy LS (1999) Simian AIDS-associated lymphoma in rhesus and cynomolgus monkeys recapitulates the primary pathobiological features of AIDS-associated non-Hodgkin’s lymphoma. AIDS Res Hum Retroviruses 15:1389–1398PubMedCrossRefGoogle Scholar
  33. Habis A, Baskin G, Simpson L, Fortgang I, Murphey-Corb M, Levy LS (2000) Rhesus lymphocryptovirus infection during the progression of SAIDS and SAIDS-associated lymphoma in the rhesus macaque. AIDS Res Hum Retroviruses 16:163–171PubMedCrossRefGoogle Scholar
  34. Hartley DA, Cooper GM (2000) Direct binding and activation of STAT transcription factors by the herpesvirus saimiri protein tip. J Biol Chem 275:16925–16932PubMedCrossRefGoogle Scholar
  35. Isakov N, Biesinger B (2000) Lck protein tyrosine kinase is a key regulator of T-cell activation and a target for signal intervention by Herpesvirus saimiri and other viral gene products. Eur J Biochem 267:3413–3421PubMedCrossRefGoogle Scholar
  36. Jiang H, Cho YG, Wang F (2000) Structural, functional, and genetic comparisons of Epstein–Barr virus nuclear antigen 3A, 3B, and 3 C homologues encoded by the rhesus lymphocryptovirus. J Virol 74:5921–5932PubMedCrossRefGoogle Scholar
  37. Jung JU, Desrosiers RC (1991) Identification and characterization of the herpesvirus saimiri oncoprotein STP-C488. J Virol 65:6953–6960PubMedGoogle Scholar
  38. Jung JU, Trimble JJ, King NW, Biesinger B, Fleckenstein BW, Desrosiers RC (1991) Identification of transforming genes of subgroup A and C strains of Herpesvirus saimiri. Proc Natl Acad Sci USA 88:7051–7055PubMedCrossRefGoogle Scholar
  39. Jung JU, Desrosiers RC (1995) Association of the viral oncoprotein STP-C488 with cellular ras. Mol Cell Biol 15:6506–6512PubMedGoogle Scholar
  40. Kaleeba JA, Bergquam EP, Wong SW (1999) A rhesus macaque rhadinovirus related to Kaposi’s sarcoma-associated herpesvirus/human herpesvirus 8 encodes a functional homologue of interleukin-6. J Virol 73:6177–6181PubMedGoogle Scholar
  41. Kalter SS, Heberling RL, Ratner JJ (1972) EBV antibody in sera of non-human primates. Nature 238:353–354PubMedCrossRefGoogle Scholar
  42. Lacoste V, Mauclere P, Dubreuil G, Lewis J, Georges-Courbot MC, Gessain A (2000a) KSHV-like herpesviruses in chimps and gorillas. Nature 407:151–152PubMedCrossRefGoogle Scholar
  43. Lacoste V, Mauclere P, Dubreuil G, Lewis J, Georges-Courbot MC, Rigoulet J, Petit T, Gessain A (2000b) Simian homologues of human gamma-2 and betaherpesviruses in mandrill and drill monkeys. J Virol 74:11993–11999PubMedCrossRefGoogle Scholar
  44. Landon JC, Malan LB (1971) Seroepidemiologic studies of Epstein–Barr virus antibody in monkeys. J Natl Cancer Inst 46:881–884PubMedGoogle Scholar
  45. Lee H, Choi JK, Li M, Kaye K, Kieff E, Jung JU (1999) Role of cellular tumor necrosis factor receptor-associated factors in NF-kappaB activation and lymphocyte transformation by herpesvirus Saimiri STP. J Virol 73:3913–3919PubMedGoogle Scholar
  46. Levy JA, Levy SB, Hirshaut Y, Kafuko G, Prince A (1971) Presence of EBV antibodies in sera from wild chimpanzees. Nature 233:559–560PubMedCrossRefGoogle Scholar
  47. Li M, Lee H, Yoon DW, Albrecht JC, Fleckenstein B, Neipel F, Jung JU (1997) Kaposi’s sarcoma-associated herpesvirus encodes a functional cyclin. J Virol 71:1984–1991PubMedGoogle Scholar
  48. Lund TC, Garcia R, Medveczky MM, Jove R, Medveczky PG (1997) Activation of STAT transcription factors by herpesvirus Saimiri Tip-484 requires p56lck. J Virol 71:6677–6682PubMedGoogle Scholar
  49. McManus MT (2003) MicroRNAs and cancer. Semin Cancer Biol 13:253–258PubMedCrossRefGoogle Scholar
  50. Melendez LV, Daniel MD, Hunt RD, Garcia FG (1968) An apparently new herpesvirus from primary kidney cultures of the squirrel monkey (Saimiri sciureus). Lab Anim Care 18:374–381PubMedGoogle Scholar
  51. Moghaddam A, Rosenzweig M, Lee-Parritz D, Annis B, Johnson RP, Wang F (1997) An animal model for acute and persistent Epstein–Barr virus infection. Science 276:2030–2033PubMedCrossRefGoogle Scholar
  52. Moghaddam A, Koch J, Annis B, Wang F (1998) Infection of human B lymphocytes with lymphocryptoviruses related to Epstein–Barr virus. J Virol 72:3205–3212PubMedGoogle Scholar
  53. Naito M, Ono K, Doi T, Kato S, Tanabe S (1971) Antibodies in human and monkey sera to herpes-type virus from a chicken with Marek’s disease and to EB virus detected by the immunofluorescence test. Biken J 14:161–166PubMedGoogle Scholar
  54. Oksenhendler E, Boulanger E, Galicier L, Du MQ, Dupin N, Diss TC, Hamoudi R, Daniel MT, Agbalika F, Boshoff C, Clauvel JP, Isaacson PG, Meignin V (2002) High incidence of Kaposi sarcoma-associated herpesvirus-related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease. Blood 99:2331–2336PubMedCrossRefGoogle Scholar
  55. Orzechowska BU, Powers MF, Sprague J, Li H, Yen B, Searles RP, Axthelm MK, Wong SW (2008) Rhesus macaque rhadinovirus-associated non-Hodgkin lymphoma: animal model for KSHV-associated malignancies. Blood 112:4227–4234PubMedCrossRefGoogle Scholar
  56. Orzechowska BU, Manoharan M, Sprague J, Estep RD, Axthelm MK, Wong SW (2009) Viral interleukin-6 encoded by rhesus macaque rhadinovirus is associated with lymphoproliferative disorder (LPD). J Med Primatol 38(Suppl 1):2–7PubMedCrossRefGoogle Scholar
  57. Peng R, Gordadze AV, Fuentes Panana EM, Wang F, Zong J, Hayward GS, Tan J, Ling PD (2000) Sequence and functional analysis of EBNA-LP and EBNA2 proteins from nonhuman primate lymphocryptoviruses. J Virol 74:379–389PubMedCrossRefGoogle Scholar
  58. Renne R, Dittmer D, Kedes D, Schmidt K, Desrosiers RC, Luciw PA, Ganem D (2004) Experimental transmission of Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) to SIV-positive and SIV-negative rhesus macaques. J Med Primatol 33:1–9PubMedCrossRefGoogle Scholar
  59. Rivailler P, Jiang H, Cho YG, Quink C, Wang F (2002) Complete nucleotide sequence of the rhesus lymphocryptovirus: genetic validation for an Epstein–Barr virus animal model. J Virol 76:421–426PubMedCrossRefGoogle Scholar
  60. Rivailler P, Carville A, Kaur A, Rao P, Quink C, Kutok JL, Westmoreland S, Klumpp S, Simon M, Aster JC, Wang F (2004) Experimental rhesus lymphocryptovirus infection in immunosuppressed macaques: an animal model for Epstein–Barr virus pathogenesis in the immunosuppressed host. Blood 104:1482–1489PubMedCrossRefGoogle Scholar
  61. Sarid R, Sato T, Bohenzky RA, Russo JJ, Chang Y (1997) Kaposi’s sarcoma-associated herpesvirus encodes a functional bcl-2 homologue. Nat Med 3:293–298PubMedCrossRefGoogle Scholar
  62. Schafer A, Cai X, Bilello JP, Desrosiers RC, Cullen BR (2007) Cloning and analysis of microRNAs encoded by the primate gamma-herpesvirus rhesus monkey rhadinovirus. Virology 364:21–27PubMedCrossRefGoogle Scholar
  63. Searles RP, Bergquam EP, Axthelm MK, Wong SW (1999) Sequence and genomic analysis of a Rhesus macaque rhadinovirus with similarity to Kaposi’s sarcoma-associated herpesvirus/human herpesvirus 8. J Virol 73:3040–3053PubMedGoogle Scholar
  64. Shibata D, Weiss LM, Hernandez AM, Nathwani BN, Bernstein L, Levine AM (1993) Epstein–Barr virus-associated non-Hodgkin’s lymphoma in patients infected with the human immunodeficiency virus. Blood 81:2102–2109PubMedGoogle Scholar
  65. Siler CA, Raab-Traub N (2008) Rhesus lymphocryptovirus latent membrane protein 2A activates beta-catenin signaling and inhibits differentiation in epithelial cells. Virology 377:273–279PubMedCrossRefGoogle Scholar
  66. Simas JP, Efstathiou S (1998) Murine gammaherpesvirus 68: a model for the study of gammaherpesvirus pathogenesis. Trends Microbiol 6:276–282PubMedCrossRefGoogle Scholar
  67. Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D, Babinet P, d’Agay MF, Clauvel JP, Raphael M, Degos L et al (1995) Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood 86:1276–1280PubMedGoogle Scholar
  68. Staskus KA, Sun R, Miller G, Racz P, Jaslowski A, Metroka C, Brett-Smith H, Haase AT (1999) 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 73:4181–4187PubMedGoogle Scholar
  69. Tsygankov AY (2005) Cell transformation by Herpesvirus saimiri. J Cell Physiol 203:305–318PubMedCrossRefGoogle Scholar
  70. Umbach JL, Strelow LI, Wong SW, Cullen BR (2010) Analysis of rhesus rhadinovirus microRNAs expressed in virus-induced tumors from infected rhesus macaques. Virology 405:592–599PubMedCrossRefGoogle Scholar
  71. Wang F, Rivailler P, Rao P, Cho Y (2001) Simian homologues of Epstein–Barr virus. Philos Trans R Soc Lond B Biol Sci 356:489–497PubMedCrossRefGoogle Scholar
  72. Wehner LE, Schroder N, Kamino K, Friedrich U, Biesinger B, Ruther U (2001) Herpesvirus saimiri Tip gene causes T-cell lymphomas in transgenic mice. DNA Cell Biol 20:81–88PubMedCrossRefGoogle Scholar
  73. Wen KW, Damania B (2010) Kaposi sarcoma-associated herpesvirus (KSHV): molecular biology and oncogenesis. Cancer Lett 289:140–150PubMedCrossRefGoogle Scholar
  74. Wiese N, Tsygankov AY, Klauenberg U, Bolen JB, Fleischer B, Broker BM (1996) Selective activation of T cell kinase p56lck by Herpesvirus saimiri protein tip. J Biol Chem 271:847–852PubMedCrossRefGoogle Scholar
  75. Wong SW, Bergquam EP, Swanson RM, Lee FW, Shiigi SM, Avery NA, Fanton JW, Axthelm MK (1999) Induction of B cell hyperplasia in simian immunodeficiency virus-infected rhesus macaques with the simian homologue of Kaposi’s sarcoma-associated herpesvirus. J Exp Med 190:827–840PubMedCrossRefGoogle Scholar
  76. Yoon DW, Lee H, Seol W, DeMaria M, Rosenzweig M, Jung JU (1997) Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation. Immunity 6:571–582PubMedCrossRefGoogle Scholar
  77. Young LS, Murray PG (2003) Epstein–Barr virus and oncogenesis: from latent genes to tumours. Oncogene 22:5108–5121PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Vaccine and Gene Therapy InstituteOregon Health & Science UniversityBeavertonUSA
  2. 2.Division of Pathobiology and ImmunologyOregon National Primate Research CenterBeavertonUSA
  3. 3.Department of Molecular Microbiology and ImmunologyOregon Health & Science UniversityPortlandUSA

Personalised recommendations