1887

Journal of General Virology header logo

Volume 87, Issue 5

Regulation of intracellular signalling by the terminal membrane proteins of members of the Free

Abstract

The human -herpesvirus Epstein–Barr virus (EBV) and the -herpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV), rhesus rhadinovirus (RRV), herpesvirus saimiri (HVS) and herpesvirus ateles (HVA) all contain genes located adjacent to the terminal-repeat region of their genomes, encoding membrane proteins involved in signal transduction. Designated ‘terminal membrane proteins' (TMPs) because of their localization in the viral genome, they interact with a variety of cellular signalling molecules, such as non-receptor protein tyrosine kinases, tumour-necrosis factor receptor-associated factors, Ras and Janus kinase (JAK), thereby initiating further downstream signalling cascades, such as the MAPK, PI3K/Akt, NF-B and JAK/STAT pathways. In the case of TMPs expressed during latent persistence of EBV and HVS (LMP1, LMP2A, Stp and Tip), their modulation of intracellular signalling pathways has been linked to the provision of survival signals to latently infected cells and, hence, a contribution to occasional cellular transformation. In contrast, activation of similar pathways by TMPs of KSHV (K1 and K15) and RRV (R1), expressed during lytic replication, may extend the lifespan of virus-producing cells, alter their migration and/or modulate antiviral immune responses. Whether R1 and K1 contribute to the oncogenic properties of KSHV and RRV has not been established satisfactorily, despite their transforming qualities in experimental settings.

  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81598-0
2006-05-01
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/5/1047.html?itemId=/content/journal/jgv/10.1099/vir.0.81598-0&mimeType=html&fmt=ahah

References

  1. Ahsan N., Kanda T., Nagashima K., Takada K. 2005; Epstein-Barr virus transforming protein LMP1 plays a critical role in virus production. J Virol 79:4415–4424 [CrossRef]
     [Google Scholar]
  2. Albrecht J.-C. 2000; Primary structure of the Herpesvirus ateles genome. J Virol 74:1033–1037 [CrossRef]
     [Google Scholar]
  3. Albrecht J.-C., Friedrich U., Kardinal C., Koehn J., Fleckenstein B., Feller S. M., Biesinger B. 1999; Herpesvirus ateles gene product Tio interacts with nonreceptor protein tyrosine kinases. J Virol 73:4631–4639
     [Google Scholar]
  4. Albrecht J.-C., Biesinger B., Muller-Fleckenstein I., Lengenfelder D., Schmidt M., Fleckenstein B., Ensser A. 2004; Herpesvirus ateles Tio can replace herpesvirus saimiri StpC and Tip oncoproteins in growth transformation of monkey and human T cells. J Virol 78:9814–9819 [CrossRef]
     [Google Scholar]
  5. Albrecht J.-C., Müller-Fleckenstein I., Schmidt M., Fleckenstein B., Biesinger B. 2005; Tyrosine phosphorylation of the Tio oncoprotein is essential for transformation of primary human T cells. J Virol 79:10507–10513 [CrossRef]
     [Google Scholar]
  6. Alexander L., Denekamp L., Knapp A., Auerbach M. R., Damania B., Desrosiers R. C. 2000; The primary sequence of rhesus monkey rhadinovirus isolate 26-95: sequence similarities to Kaposi's sarcoma-associated herpesvirus and rhesus monkey rhadinovirus isolate 17577. J Virol 74:3388–3398 [CrossRef]
     [Google Scholar]
  7. Allen M. D., Young L. S., Dawson C. W. 2005; The Epstein-Barr virus-encoded LMP2A and LMP2B proteins promote epithelial cell spreading and motility. J Virol 79:1789–1802 [CrossRef]
     [Google Scholar]
  8. Ardila-Osorio H., Clausse B., Mishal Z., Wiels J., Tursz T., Busson P. 1999; Evidence of LMP1-TRAF3 interactions in glycosphingolipid-rich complexes of lymphoblastoid and nasopharyngeal carcinoma cells. Int J Cancer 81:645–649 [CrossRef]
     [Google Scholar]
  9. Atkinson P. G. P., Coope H. J., Rowe M., Ley S. C. 2003; Latent membrane protein 1 of Epstein-Barr virus stimulates processing of NF- κ B2 p100 to p52. J Biol Chem 278:51134–51142 [CrossRef]
     [Google Scholar]
  10. Baichwal V. R., Sugden B. 1988; Transformation of Balb 3T3 cells by the BNLF-1 gene of Epstein-Barr virus. Oncogene 2:461–467
     [Google Scholar]
  11. Baichwal V. R., Sugden B. 1989; The multiple membrane-spanning segments of the BNLF-1 oncogene from Epstein-Barr virus are required for transformation. Oncogene 4:67–74
     [Google Scholar]
  12. Bauer F., Hofinger E., Hoffmann S., Rösch P., Schweimer K., Sticht H. 2004; Characterization of Lck-binding elements in the herpesviral regulatory Tip protein. Biochemistry 43:14932–14939 [CrossRef]
     [Google Scholar]
  13. Benschop R. J., Cambier J. C. 1999; B cell development: signal transduction by antigen receptors and their surrogates. Curr Opin Immunol 11:143–151 [CrossRef]
     [Google Scholar]
  14. Bergquam E. P., Avery N., Shiigi S. M., Axthelm M. K., Wong S. W. 1999; Rhesus rhadinovirus establishes a latent infection in B lymphocytes in vivo. J Virol 73:7874–7876
     [Google Scholar]
  15. Biesinger B., Trimble J. J., Desrosiers R. C., Fleckenstein B. 1990; The divergence between two oncogenic Herpesvirus saimiri strains in a genomic region related to the transforming phenotype. Virology 176:505–514 [CrossRef]
     [Google Scholar]
  16. Biesinger B., Muller-Fleckenstein I., Simmer B., Lang G., Wittmann S., Platzer E., Desrosiers R. C., Fleckenstein B. 1992; Stable growth transformation of human T lymphocytes by Herpesvirus saimiri. Proc Natl Acad Sci U S A 89:3116–3119 [CrossRef]
     [Google Scholar]
  17. Biesinger B., Tsygankov A. Y., Fickenscher H., Emmrich F., Fleckenstein B., Bolen J. B., Bröker B. M. 1995; The product of the Herpesvirus saimiri open reading frame 1 (tip) interacts with T cell-specific kinase p56 lck in transformed cells. J Biol Chem 270:4729–4734 [CrossRef]
     [Google Scholar]
  18. Birkenbach M., Liebowitz D., Wang F., Sample J., Kieff E. 1989; Epstein-Barr virus latent infection membrane protein increases vimentin expression in human B-cell lines. J Virol 63:4079–4084
     [Google Scholar]
  19. Boos H., Berger R., Kuklik-Roos C., Iftner T., Mueller-Lantzsch N. 1987; Enhancement of Epstein-Barr virus membrane protein (LMP) expression by serum, TPA, or n -butyrate in latently infected Raji cells. Virology 159:161–165 [CrossRef]
     [Google Scholar]
  20. Brinkmann M. M., Glenn M., Rainbow L., Kieser A., Henke-Gendo C., Schulz T. F. 2003; Activation of mitogen-activated protein kinase and NF- κ B pathways by a Kaposi's sarcoma-associated herpesvirus K15 membrane protein. J Virol 77:9346–9358 [CrossRef]
     [Google Scholar]
  21. Brodeur S. R., Cheng G., Baltimore D., Thorley-Lawson D. A. 1997; Localization of the major NF- κ B-activating site and the sole TRAF3 binding site of LMP-1 defines two distinct signaling motifs. J Biol Chem 272:19777–19784 [CrossRef]
     [Google Scholar]
  22. Bröker B. M., Tsygankov A. Y., Müller-Fleckenstein I., Guse A. H., Chitaev N. A., Biesinger B., Fleckenstein B., Emmrich F. 1993; Immortalization of human T cell clones by Herpesvirus saimiri . Signal transduction analysis reveals functional CD3, CD4, and IL-2 receptors. J Immunol 151:1184–1192
     [Google Scholar]
  23. Burkhardt A. L., Bolen J. B., Kieff E., Longnecker R. 1992; An Epstein-Barr virus transformation-associated membrane protein interacts with src family tyrosine kinases. J Virol 66:5161–5167
     [Google Scholar]
  24. Cahir McFarland E. D., Izumi K. M., Mosialos G. 1999; Epstein-Barr virus transformation: involvement of latent membrane protein 1-mediated activation of NF- κ B. Oncogene 18:6959–6964 [CrossRef]
     [Google Scholar]
  25. Cahir McFarland E. D., Davidson D. M., Schauer S. L., Duong J., Kieff E. 2000; NF- κ B inhibition causes spontaneous apoptosis in Epstein-Barr virus-transformed lymphoblastoid cells. Proc Natl Acad Sci U S A 97:6055–6060 [CrossRef]
     [Google Scholar]
  26. Cahir McFarland E. D., Carter K., Rosenwald A., Giltnane J. M., Henrickson S. E., Staudt L. M., Kieff E. 2004; Role of NF- κ B in cell survival and transcription of latent membrane protein 1-expressing or Epstein-Barr virus latency III-infected cells. J Virol 78:4108–4119 [CrossRef]
     [Google Scholar]
  27. Caldwell R. G., Wilson J. B., Anderson S. J., Longnecker R. 1998; Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity 9:405–411 [CrossRef]
     [Google Scholar]
  28. Caldwell R. G., Brown R. C., Longnecker R. 2000; Epstein-Barr virus LMP2A-induced B-cell survival in two unique classes of EμLMP2A transgenic mice. J Virol 74:1101–1113 [CrossRef]
     [Google Scholar]
  29. Chang Y., Cesarman E., Pessin M. S., Lee F., Culpepper J., Knowles D. M., Moore P. S. 1994; Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266:1865–1869 [CrossRef]
     [Google Scholar]
  30. Chang Y., Lee H.-H., Chang S.-S., Hsu T.-Y., Wang P.-W., Chang Y.-S., Takada K., Tsai C.-H. 2004; Induction of Epstein-Barr virus latent membrane protein 1 by a lytic transactivator Rta. J Virol 78:13028–13036 [CrossRef]
     [Google Scholar]
  31. Chen H., Lee J. M., Wang Y., Huang D. P., Ambinder R. F., Hayward S. D. 1999; The Epstein-Barr virus latency Bam HI-Q promoter is positively regulated by STATs and Zta interference with JAK/STAT activation leads to loss of Bam HI-Q promoter activity. Proc Natl Acad Sci U S A 96:9339–9344 [CrossRef]
     [Google Scholar]
  32. Chen H., Lee J. M., Zong Y., Borowitz M., Ng M. H., Ambinder R. F., Hayward S. D. 2001; Linkage between STAT regulation and Epstein-Barr virus gene expression in tumors. J Virol 75:2929–2937 [CrossRef]
     [Google Scholar]
  33. Chen S.-Y., Lu J., Shih Y.-C., Tsai C.-H. 2002; Epstein-Barr virus latent membrane protein 2A regulates c-Jun protein through extracellular signal-regulated kinase. J Virol 76:9556–9561 [CrossRef]
     [Google Scholar]
  34. Chen H., Hutt-Fletcher L., Cao L., Hayward S. D. 2003; A positive autoregulatory loop of LMP1 expression and STAT activation in epithelial cells latently infected with Epstein-Barr virus. J Virol 77:4139–4148 [CrossRef]
     [Google Scholar]
  35. Cho N.-H., Feng P., Lee S.-H., Lee B.-S., Liang X., Chang H., Jung J. U. 2004; Inhibition of T cell receptor signal transduction by tyrosine kinase-interacting protein of herpesvirus saimiri. J Exp Med 200:681–687 [CrossRef]
     [Google Scholar]
  36. Choi J.-K., Lee B.-S., Shim S. N., Li M., Jung J. U. 2000a; Identification of the novel K15 gene at the rightmost end of the Kaposi's sarcoma-associated herpesvirus genome. J Virol 74:436–446 [CrossRef]
     [Google Scholar]
  37. Choi J.-K., Ishido S., Jung J. U. 2000b; The collagen repeat sequence is a determinant of the degree of herpesvirus saimiri STP transforming activity. J Virol 74:8102–8110 [CrossRef]
     [Google Scholar]
  38. Chung Y.-H., Cho N.-H., Garcia M. I., Lee S.-H., Feng P., Jung J. U. 2004; Activation of Stat3 transcription factor by Herpesvirus saimiri STP-A oncoprotein. J Virol 78:6489–6497 [CrossRef]
     [Google Scholar]
  39. Clausse B., Fizazi K., Walczak V., Tetaud C., Wiels J., Tursz T., Busson P. 1997; High concentration of the EBV latent membrane protein 1 in glycosphingolipid-rich complexes from both epithelial and lymphoid cells. Virology 228:285–293 [CrossRef]
     [Google Scholar]
  40. Contreras-Salazar B., Ehlin-Henriksson B., Klein G., Masucci M. G. 1990; Up regulation of the Epstein-Barr virus (EBV)-encoded membrane protein LMP in the Burkitt's lymphoma line Daudi after exposure to n -butyrate and after EBV superinfection. J Virol 64:5441–5447
     [Google Scholar]
  41. Cook P. M., Whitby D., Calabro M.-L. & 7 other authors 1999; Variability and evolution of Kaposi's sarcoma-associated herpesvirus in Europe and Africa. International Collaborative Group. AIDS 13:1165–1176 [CrossRef]
     [Google Scholar]
  42. Cook R. D., Hodgson T. A., Waugh A. C. W., Molyneux E. M., Borgstein E., Sherry A., Teo C. G., Porter S. R. 2002; Mixed patterns of transmission of human herpesvirus-8 (Kaposi's sarcoma-associated herpesvirus) in Malawian families. J Gen Virol 83:1613–1619
     [Google Scholar]
  43. Dadgostar H., Zarnegar B., Hoffmann A., Qin X.-F., Truong U., Rao G., Baltimore D., Cheng G. 2002; Cooperation of multiple signaling pathways in CD40-regulated gene expression in B lymphocytes. Proc Natl Acad Sci U S A 99:1497–1502 [CrossRef]
     [Google Scholar]
  44. Damania B., Li M., Choi J.-K., Alexander L., Jung J. U., Desrosiers R. C. 1999; Identification of the R1 oncogene and its protein product from the rhadinovirus of rhesus monkeys. J Virol 73:5123–5131
     [Google Scholar]
  45. Damania B., DeMaria M., Jung J. U., Desrosiers R. C. 2000; Activation of lymphocyte signaling by the R1 protein of rhesus monkey rhadinovirus. J Virol 74:2721–2730 [CrossRef]
     [Google Scholar]
  46. Daniel M. D., Melendez L. V., Hunt R. D., King N. W., Anver M., Fraser C. E., Barahona H., Baggs R. B. 1974; Herpesvirus saimiri : VII. Induction of malignant lymphoma in New Zealand white rabbits. J Natl Cancer Inst 53:1803–1807
     [Google Scholar]
  47. Dawson C. W., Rickinson A. B., Young L. S. 1990; Epstein-Barr virus latent membrane protein inhibits human epithelial cell differentiation. Nature 344:777–780 [CrossRef]
     [Google Scholar]
  48. Dawson C. W., Tramountanis G., Eliopoulos A. G., Young L. S. 2003; Epstein-Barr virus latent membrane protein 1 (LMP1) activates the phosphatidylinositol 3-kinase/Akt pathway to promote cell survival and induce actin filament remodeling. J Biol Chem 278:3694–3704 [CrossRef]
     [Google Scholar]
  49. Desrosiers R. C., Falk L. A. 1982; Herpesvirus saimiri strain variability. J Virol 43:352–356
     [Google Scholar]
  50. Desrosiers R. C., Bakker A., Kamine J., Falk L. A., Hunt R. D., King N. W. 1985; A region of the Herpesvirus saimiri genome required for oncogenicity. Science 228:184–187 [CrossRef]
     [Google Scholar]
  51. Desrosiers R. C., Silva D. P., Waldron L. M., Letvin N. L. 1986; Nononcogenic deletion mutants of herpesvirus saimiri are defective for in vitro immortalization. J Virol 57:701–705
     [Google Scholar]
  52. Desrosiers R. C., Sasseville V. G., Czajak S. C., Zhang X., Mansfield K. G., Kaur A., Johnson R. P., Lackner A. A., Jung J. U. 1997; A herpesvirus of rhesus monkeys related to the human Kaposi's sarcoma-associated herpesvirus. J Virol 71:9764–9769
     [Google Scholar]
  53. Devergne O., Hatzivassiliou E., Izumi K. M., Kaye K. M., Kleijnen M. F., Kieff E., Mosialos G. 1996; Association of TRAF1, TRAF2, and TRAF3 with an Epstein-Barr virus LMP1 domain important for B-lymphocyte transformation: role in NF- κ B activation. Mol Cell Biol 16:7098–7108
     [Google Scholar]
  54. Devergne O., Cahir McFarland E. D., Mosialos G., Izumi K. M., Ware C. F., Kieff E. 1998; Role of the TRAF binding site and NF- κ B activation in Epstein-Barr virus latent membrane protein 1-induced cell gene expression. J Virol 72:7900–7908
     [Google Scholar]
  55. Dirmeier U., Neuhierl B., Kilger E., Reisbach G., Sandberg M. L., Hammerschmidt W. 2003; Latent membrane protein 1 is critical for efficient growth transformation of human B cells by epstein-barr virus. Cancer Res 63:2982–2989
     [Google Scholar]
  56. Dirmeier U., Hoffmann R., Kilger E. & 7 other authors 2005; Latent membrane protein 1 of Epstein–Barr virus coordinately regulates proliferation with control of apoptosis. Oncogene 24:1711–1717 [CrossRef]
     [Google Scholar]
  57. Douglas J., Dutia B., Rhind S., Stewart J. P., Talbot S. J. 2004; Expression in a recombinant murid herpesvirus 4 reveals the in vivo transforming potential of the K1 open reading frame of Kaposi's sarcoma-associated herpesvirus. J Virol 78:8878–8884 [CrossRef]
     [Google Scholar]
  58. D'Souza B. N., Edelstein L. C., Pegman P. M. & 7 other authors 2004; Nuclear factor κ B-dependent activation of the antiapoptotic bfl-1 gene by the Epstein-Barr virus latent membrane protein 1 and activated CD40 receptor. J Virol 78:1800–1816 [CrossRef]
     [Google Scholar]
  59. Duboise S. M., Guo J., Czajak S., Desrosiers R. C., Jung J. U. 1998a; STP and Tip are essential for herpesvirus saimiri oncogenicity. J Virol 72:1308–1313
     [Google Scholar]
  60. Duboise S. M., Lee H., Guo J., Choi J. K., Czajak S., Simon M., Desrosiers R. C., Jung J. U. 1998b; Mutation of the Lck-binding motif of Tip enhances lymphoid cell activation by herpesvirus saimiri. J Virol 72:2607–2614
     [Google Scholar]
  61. Durie F. H., Foy T. M., Masters S. R., Laman J. D., Noelle R. J. 1994; The role of CD40 in the regulation of humoral and cell-mediated immunity. Immunol Today 15:406–411 [CrossRef]
     [Google Scholar]
  62. Dykstra M. L., Longnecker R., Pierce S. K. 2001; Epstein–Barr virus coopts lipid rafts to block the signaling and antigen transport functions of the BCR. Immunity 14:57–67 [CrossRef]
     [Google Scholar]
  63. Eliopoulos A. G., Young L. S. 1998; Activation of the cJun N-terminal kinase (JNK) pathway by the Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Oncogene 16:1731–1742 [CrossRef]
     [Google Scholar]
  64. Eliopoulos A. G., Young L. S. 2001; LMP1 structure and signal transduction. Semin Cancer Biol 11:435–444 [CrossRef]
     [Google Scholar]
  65. Eliopoulos A. G., Stack M., Dawson C. W., Kaye K. M., Hodgkin L., Sihota S., Rowe M., Young L. S. 1997; Epstein–Barr virus-encoded LMP1 and CD40 mediate IL-6 production in epithelial cells via an NF- κ B pathway involving TNF receptor-associated factors. Oncogene 14:2899–2916 [CrossRef]
     [Google Scholar]
  66. Eliopoulos A. G., Gallagher N. J., Blake S. M. S., Dawson C. W., Young L. S. 1999a; Activation of the p38 mitogen-activated protein kinase pathway by Epstein-Barr virus-encoded latent membrane protein 1 coregulates interleukin-6 and interleukin-8 production. J Biol Chem 274:16085–16096 [CrossRef]
     [Google Scholar]
  67. Eliopoulos A. G., Blake S. M. S., Floettmann J. E., Rowe M., Young L. S. 1999b; Epstein-Barr virus-encoded latent membrane protein 1 activates the JNK pathway through its extreme C terminus via a mechanism involving TRADD and TRAF2. J Virol 73:1023–1035
     [Google Scholar]
  68. Engels N., Merchant M., Pappu R., Chan A. C., Longnecker R., Wienands J. 2001; Epstein-Barr virus latent membrane protein 2A (LMP2A) employs the SLP-65 signaling module. J Exp Med 194:255–264 [CrossRef]
     [Google Scholar]
  69. Ensser A., Fleckenstein B. 2005; T-cell transformation and oncogenesis by γ 2-herpesviruses. Adv Cancer Res 93:91–128
     [Google Scholar]
  70. Everly D. N. Jr, Mainou B. A., Raab-Traub N. 2004; Induction of Id1 and Id3 by latent membrane protein 1 of Epstein-Barr virus and regulation of p27/Kip and cyclin-dependent kinase 2 in rodent fibroblast transformation. J Virol 78:13470–13478 [CrossRef]
     [Google Scholar]
  71. Fahraeus R., Rymo L., Rhim J. S., Klein G. 1990; Morphological transformation of human keratinocytes expressing the LMP gene of Epstein-Barr virus. Nature 345:447–449 [CrossRef]
     [Google Scholar]
  72. Fahraeus R., Chen W., Trivedi P., Klein G., Obrink B. 1992; Decreased expression of E-cadherin and increased invasive capacity in EBV-LMP-transfected human epithelial and murine adenocarcinoma cells. Int J Cancer 52:834–838 [CrossRef]
     [Google Scholar]
  73. Fairbairn L. J., Stewart J. P., Hampson I. N., Arrand J. R., Dexter T. M. 1993; Expression of Epstein–Barr virus latent membrane protein influences self-renewal and differentiation in a multipotential murine haemopoietic ‘stem cell’ line. J Gen Virol 74:247–254 [CrossRef]
     [Google Scholar]
  74. Falk L. A., Wolfe L. G., Deinhardt F. 1972; Isolation of Herpesvirus saimiri from blood of squirrel monkeys ( Saimiri sciureus ). J Natl Cancer Inst 48:1499–1505
     [Google Scholar]
  75. Faqing T., Zhi H., Liqun Y., Min T., Huanhua G., Xiyun D., Ya C. 2005; Epstein–Barr virus LMP1 initiates cell proliferation and apoptosis inhibition via regulating expression of survivin in nasopharyngeal carcinoma. Exp Oncol 27:96–101
     [Google Scholar]
  76. Farrell P. J. 1995; Epstein-Barr virus immortalizing genes. Trends Microbiol 3:105–109 [CrossRef]
     [Google Scholar]
  77. Fennewald S., van Santen V., Kieff E. 1984; Nucleotide sequence of an mRNA transcribed in latent growth-transforming virus infection indicates that it may encode a membrane protein. J Virol 51:411–419
     [Google Scholar]
  78. Fickenscher H., Fleckenstein B. 2001; Herpesvirus saimiri . Philos Trans R Soc Lond B Biol Sci 356:545–567 [CrossRef]
     [Google Scholar]
  79. Fickenscher H., Bökel C., Knappe A., Biesinger B., Meinl E., Fleischer B., Fleckenstein B., Bröker B. M. 1997; Functional phenotype of transformed human αβ and γδ T cells determined by different subgroup C strains of herpesvirus saimiri. J Virol 71:2252–2263
     [Google Scholar]
  80. Flanagan J., Middeldorp J., Sculley T. 2003; Localization of the Epstein–Barr virus protein LMP 1 to exosomes. J Gen Virol 84:1871–1879 [CrossRef]
     [Google Scholar]
  81. Floettmann J. E., Rowe M. 1997; Epstein-Barr virus latent membrane protein-1 (LMP1) C-terminus activation region 2 (CTAR2) maps to the far C-terminus and requires oligomerisation for NF- κ B activation. Oncogene 15:1851–1858 [CrossRef]
     [Google Scholar]
  82. Floettmann J. E., Eliopoulos A. G., Jones M., Young L. S., Rowe M. 1998; Epstein–Barr virus latent membrane protein-1 (LMP1) signalling is distinct from CD40 and involves physical cooperation of its two C-terminus functional regions. Oncogene 17:2383–2392 [CrossRef]
     [Google Scholar]
  83. Franken M., Devergne O., Rosenzweig M., Annis B., Kieff E., Wang F. 1996; Comparative analysis identifies conserved tumor necrosis factor receptor-associated factor 3 binding sites in the human and simian Epstein-Barr virus oncogene LMP1. J Virol 70:7819–7826
     [Google Scholar]
  84. Fries K. L., Miller W. E., Raab-Traub N. 1996; Epstein-Barr virus latent membrane protein 1 blocks p53-mediated apoptosis through the induction of the A20 gene. J Virol 70:8653–8659
     [Google Scholar]
  85. Fruehling S., Longnecker R. 1997; The immunoreceptor tyrosine-based activation motif of Epstein–Barr virus LMP2A is essential for blocking BCR-mediated signal transduction. Virology 235:241–251 [CrossRef]
     [Google Scholar]
  86. Fruehling S., Lee S. K., Herrold R., Frech B., Laux G., Kremmer E., Grasser F. A., Longnecker R. 1996; Identification of latent membrane protein 2A (LMP2A) domains essential for the LMP2A dominant-negative effect on B-lymphocyte surface immunoglobulin signal transduction. J Virol 70:6216–6226
     [Google Scholar]
  87. Fruehling S., Swart R., Dolwick K. M., Kremmer E., Longnecker R. 1998; Tyrosine 112 of latent membrane protein 2A is essential for protein tyrosine kinase loading and regulation of Epstein-Barr virus latency. J Virol 72:7796–7806
     [Google Scholar]
  88. Fukuda M., Longnecker R. 2004; Latent membrane protein 2A inhibits transforming growth factor- β 1-induced apoptosis through the phosphatidylinositol 3-kinase/Akt pathway. J Virol 78:1697–1705 [CrossRef]
     [Google Scholar]
  89. Fukuda M., Longnecker R. 2005; Epstein-Barr virus (EBV) latent membrane protein 2A regulates B-cell receptor-induced apoptosis and EBV reactivation through tyrosine phosphorylation. J Virol 79:8655–8660 [CrossRef]
     [Google Scholar]
  90. Gaubatz S., Lindeman G. J., Ishida S., Jakoi L., Nevins J. R., Livingston D. M., Rempel R. E. 2000; E2F4 and E2F5 play an essential role in pocket protein-mediated G1 control. Mol Cell 6:729–735 [CrossRef]
     [Google Scholar]
  91. Geck P., Whitaker S. A., Medveczky M. M., Medveczky P. G. 1990; Expression of collagenlike sequences by a tumor virus, herpesvirus saimiri. J Virol 64:3509–3515
     [Google Scholar]
  92. Ghosh S., Karin M. 2002; Missing pieces in the NF- κ B puzzle. Cell 109:S81–S96 [CrossRef]
     [Google Scholar]
  93. Gires O., Zimber-Strobl U., Gonnella R., Ueffing M., Marschall G., Zeidler R., Pich D., Hammerschmidt W. 1997; Latent membrane protein 1 of Epstein–Barr virus mimics a constitutively active receptor molecule. EMBO J 16:6131–6140 [CrossRef]
     [Google Scholar]
  94. Gires O., Kohlhuber F., Kilger E. & 7 other authors 1999; Latent membrane protein 1 of Epstein–Barr virus interacts with JAK3 and activates STAT proteins. EMBO J 18:3064–3073 [CrossRef]
     [Google Scholar]
  95. Glenn M., Rainbow L., Auradé F., Davison A., Schulz T. F. 1999; Identification of a spliced gene from Kaposi's sarcoma-associated herpesvirus encoding a protein with similarities to latent membrane proteins 1 and 2A of Epstein-Barr virus. J Virol 73:6953–6963
     [Google Scholar]
  96. Greensill J., Schulz T. F. 2000; Rhadinoviruses (gamma2-herpesviruses) of Old World primates: models for KSHV/HHV8-associated disease?. AIDS 14 (Suppl. 3):S11–S19 [CrossRef]
     [Google Scholar]
  97. Greensill J., Sheldon J. A., Renwick N. M., Beer B. E., Norley S., Goudsmit J., Schulz T. F. 2000a; Two distinct gamma-2 herpesviruses in African green monkeys: a second gamma-2 herpesvirus lineage among Old World primates?. J Virol 74:1572–1577 [CrossRef]
     [Google Scholar]
  98. Greensill J., Sheldon J. A., Murthy K. K., Bessonette J. S., Beer B. E., Schulz T. F. 2000b; A chimpanzee rhadinovirus sequence related to Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8: increased detection after HIV-1 infection in the absence of disease. AIDS 14:F129–F135 [CrossRef]
     [Google Scholar]
  99. Gregory C. D., Dive C., Henderson S., Smith C. A., Williams G. T., Gordon J., Rickinson A. B. 1991; Activation of Epstein–Barr virus latent genes protects human B cells from death by apoptosis. Nature 349:612–614 [CrossRef]
     [Google Scholar]
  100. Guo J., Duboise M., Lee H., Li M., Choi J.-K., Rosenzweig M., Jung J. U. 1997; Enhanced downregulation of Lck-mediated signal transduction by a Y114 mutation of herpesvirus saimiri Tip. J Virol 71:7092–7096
     [Google Scholar]
  101. Guo J., Williams K., Duboise S. M., Alexander L., Veazey R., Jung J. U. 1998; Substitution of ras for the herpesvirus saimiri STP oncogene in lymphocyte transformation. J Virol 72:3698–3704
     [Google Scholar]
  102. Hammarskjöld M.-L., Simurda M. C. 1992; Epstein-Barr virus latent membrane protein transactivates the human immunodeficiency virus type 1 long terminal repeat through induction of NF- κ B activity. J Virol 66:6496–6501
     [Google Scholar]
  103. Hartley D. A., Cooper G. M. 2000; Direct binding and activation of STAT transcription factors by the herpesvirus saimiri protein Tip. J Biol Chem 275:16925–16932 [CrossRef]
     [Google Scholar]
  104. Hartley D. A., Hurley T. R., Hardwick J. S., Lund T. C., Medveczky P. G., Sefton B. M. 1999; Activation of the Lck tyrosine-protein kinase by the binding of the Tip protein of herpesvirus saimiri in the absence of regulatory tyrosine phosphorylation. J Biol Chem 274:20056–20059 [CrossRef]
     [Google Scholar]
  105. Hartley D. A., Amdjadi K., Hurley T. R., Lund T. C., Medveczky P. G., Sefton B. M. 2000; Activation of the Lck tyrosine protein kinase by the herpesvirus saimiri Tip protein involves two binding interactions. Virology 276:339–348 [CrossRef]
     [Google Scholar]
  106. Hasham M. G., Tsygankov A. Y. 2004; Tip, an Lck-interacting protein of Herpesvirus saimiri , causes Fas- and Lck-dependent apoptosis of T lymphocytes. Virology 320:313–329 [CrossRef]
     [Google Scholar]
  107. Hatzivassiliou E., Miller W. E., Raab-Traub N., Kieff E., Mosialos G. 1998; A fusion of the EBV latent membrane protein-1 (LMP1) transmembrane domains to the CD40 cytoplasmic domain is similar to LMP1 in constitutive activation of epidermal growth factor receptor expression, nuclear factor- κ B, and stress-activated protein kinase. J Immunol 160:1116–1121
     [Google Scholar]
  108. Hayward G. S. 1999; KSHV strains: the origins and global spread of the virus. Semin Cancer Biol 9:187–199 [CrossRef]
     [Google Scholar]
  109. He Z., Xin B., Yang X., Chan C., Cao L. 2000; Nuclear factor- κ B activation is involved in LMP1-mediated transformation and tumorigenesis of rat-1 fibroblasts. Cancer Res 60:1845–1848
     [Google Scholar]
  110. Heck E., Lengenfelder D., Schmidt M., Muller-Fleckenstein I., Fleckenstein B., Biesinger B., Ensser A. 2005; T-cell growth transformation by herpesvirus saimiri is independent of STAT3 activation. J Virol 79:5713–5720 [CrossRef]
     [Google Scholar]
  111. Henderson S., Rowe M., Gregory C., Croom-Carter D., Wang F., Longnecker R., Kieff E., Rickinson A. 1991; Induction of bcl -2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 65:1107–1115 [CrossRef]
     [Google Scholar]
  112. Hennessy K., Fennewald S., Hummel M., Cole T., Kieff E. 1984; A membrane protein encoded by Epstein–Barr virus in latent growth-transforming infection. Proc Natl Acad Sci U S A 81:7207–7211 [CrossRef]
     [Google Scholar]
  113. Higuchi M., Izumi K. M., Kieff E. 2001; Epstein-Barr virus latent-infection membrane proteins are palmitoylated and raft-associated: protein 1 binds to the cytoskeleton through TNF receptor cytoplasmic factors. Proc Natl Acad Sci U S A 98:4675–4680 [CrossRef]
     [Google Scholar]
  114. Higuchi M., Kieff E., Izumi K. M. 2002; The Epstein-Barr virus latent membrane protein 1 putative Janus kinase 3 (JAK3) binding domain does not mediate JAK3 association or activation in B-lymphoma or lymphoblastoid cell lines. J Virol 76:455–459 [CrossRef]
     [Google Scholar]
  115. Hör S., Ensser A., Reiss C., Ballmer-Hofer K., Biesinger B. 2001; Herpesvirus saimiri protein StpB associates with cellular Src. J Gen Virol 82:339–344
     [Google Scholar]
  116. Hu L.-F., Zabarovsky E. R., Chen F., Cao S.-L., Ernberg I., Klein G., Winberg G. 1991; Isolation and sequencing of the Epstein–Barr virus BNLF-1 gene (LMP1) from a Chinese nasopharyngeal carcinoma. J Gen Virol 72:2399–2409 [CrossRef]
     [Google Scholar]
  117. Hu L.-F., Chen F., Zheng X., Ernberg I., Cao S.-L., Christensson B., Klein G., Winberg G. 1993; Clonability and tumorigenicity of human epithelial cells expressing the EBV encoded membrane protein LMP1. Oncogene 8:1575–1583
     [Google Scholar]
  118. Hudson G. S., Farrell P. J., Barrell B. G. 1985; Two related but differentially expressed potential membrane proteins encoded by the Eco RI Dhet region of Epstein-Barr virus B95-8. J Virol 53:528–535
     [Google Scholar]
  119. Huen D. S., Henderson S. A., Croom-Carter D., Rowe M. 1995; The Epstein-Barr virus latent membrane protein-1 (LMP1) mediates activation of NF- κ B and cell surface phenotype via two effector regions in its carboxy-terminal cytoplasmic domain. Oncogene 10:549–560
     [Google Scholar]
  120. Hunt R. D., Melendez L. V., King N. W., Garcia F. G. 1972a; Herpesvirus saimiri malignant lymphoma in spider monkeys. A new susceptible host. J Med Primatol 1:114–128
     [Google Scholar]
  121. Hunt R. D., Melendez L. V., Garcia F. G., Trum B. F. 1972b; Pathologic features of Herpesvirus ateles lymphoma in cotton-topped marmosets ( Saguinus oedipus ). J Natl Cancer Inst 49:1631–1639
     [Google Scholar]
  122. Ikeda M., Ikeda A., Longan L. C., Longnecker R. 2000; The Epstein–Barr virus latent membrane protein 2A PY motif recruits WW domain-containing ubiquitin-protein ligases. Virology 268:178–191 [CrossRef]
     [Google Scholar]
  123. Ikeda M., Ikeda A., Longnecker R. 2001; PY motifs of Epstein-Barr virus LMP2A regulate protein stability and phosphorylation of LMP2A-associated proteins. J Virol 75:5711–5718 [CrossRef]
     [Google Scholar]
  124. Ikeda M., Ikeda A., Longnecker R. 2002; Lysine-independent ubiquitination of Epstein–Barr virus LMP2A. Virology 300:153–159 [CrossRef]
     [Google Scholar]
  125. Ikeda A., Caldwell R. G., Longnecker R., Ikeda M. 2003; Itchy, a Nedd4 ubiquitin ligase, downregulates latent membrane protein 2A activity in B-cell signaling. J Virol 77:5529–5534 [CrossRef]
     [Google Scholar]
  126. 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 267:3413–3421 [CrossRef]
     [Google Scholar]
  127. Izumi K. M. 2001; Identification of EBV transforming genes by recombinant EBV technology. Semin Cancer Biol 11:407–414 [CrossRef]
     [Google Scholar]
  128. Izumi K. M., Kieff E. D. 1997; The Epstein-Barr virus oncogene product latent membrane protein 1 engages the tumor necrosis factor receptor-associated death domain protein to mediate B lymphocyte growth transformation and activate NF- κ B. Proc Natl Acad Sci U S A 94:12592–12597 [CrossRef]
     [Google Scholar]
  129. Izumi K. M., Kaye K. M., Kieff E. D. 1997; The Epstein-Barr virus LMP1 amino acid sequence that engages tumor necrosis factor receptor associated factors is critical for primary B lymphocyte growth transformation. Proc Natl Acad Sci U S A 94:1447–1452 [CrossRef]
     [Google Scholar]
  130. Izumi K. M., Cahir McFarland E. D., Ting A. T., Riley E. A., Seed B., Kieff E. D. 1999a; The Epstein-Barr virus oncoprotein latent membrane protein 1 engages the tumor necrosis factor receptor-associated proteins TRADD and receptor-interacting protein (RIP) but does not induce apoptosis or require RIP for NF- κ B activation. Mol Cell Biol 19:5759–5767
     [Google Scholar]
  131. Izumi K. M., Cahir McFarland E. D., Riley E. A., Rizzo D., Chen Y., Kieff E. 1999b; The residues between the two transformation effector sites of Epstein-Barr virus latent membrane protein 1 are not critical for B-lymphocyte growth transformation. J Virol 73:9908–9916
     [Google Scholar]
  132. Jenner R. G., Albà M. M., Boshoff C., Kellam P. 2001; Kaposi's sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. J Virol 75:891–902 [CrossRef]
     [Google Scholar]
  133. Jung J. U., Desrosiers R. C. 1991; Identification and characterization of the herpesvirus saimiri oncoprotein STP-C488. J Virol 65:6953–6960
     [Google Scholar]
  134. Jung J. U., Desrosiers R. C. 1992; Herpesvirus saimiri oncogene STP-C488 encodes a phosphoprotein. J Virol 66:1777–1780
     [Google Scholar]
  135. Jung J. U., Desrosiers R. C. 1994; Distinct functional domains of STP-C488 of herpesvirus saimiri. Virology 204:751–758 [CrossRef]
     [Google Scholar]
  136. Jung J. U., Desrosiers R. C. 1995; Association of the viral oncoprotein STP-C488 with cellular ras. Mol Cell Biol 15:6506–6512
     [Google Scholar]
  137. Jung J. U., Trimble J. J., King N. W., Biesinger B., Fleckenstein B. W., Desrosiers R. C. 1991; Identification of transforming genes of subgroup A and C strains of Herpesvirus saimiri . Proc Natl Acad Sci U S A 88:7051–7055 [CrossRef]
     [Google Scholar]
  138. Jung J. U., Lang S. M., Jun T., Roberts T. M., Veillette A., Desrosiers R. C. 1995a; Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri. J Virol 69:7814–7822
     [Google Scholar]
  139. Jung J. U., Lang S. M., Friedrich U., Jun T., Roberts T. M., Desrosiers R. C., Biesinger B. 1995b; Identification of Lck-binding elements in tip of herpesvirus saimiri. J Biol Chem 270:20660–20667 [CrossRef]
     [Google Scholar]
  140. Kaye K. M., Izumi K. M., Kieff E. 1993; Epstein–Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation. Proc Natl Acad Sci U S A 90:9150–9154 [CrossRef]
     [Google Scholar]
  141. Kaye K. M., Izumi K. M., Mosialos G., Kieff E. 1995; The Epstein-Barr virus LMP1 cytoplasmic carboxy terminus is essential for B-lymphocyte transformation; fibroblast cocultivation complements a critical function within the terminal 155 residues. J Virol 69:675–683
     [Google Scholar]
  142. Kaye K. M., Devergne O., Harada J. N., Izumi K. M., Yalamanchili R., Kieff E., Mosialos G. 1996; Tumor necrosis factor receptor associated factor 2 is a mediator of NF- κ B activation by latent infection membrane protein 1, the Epstein–Barr virus transforming protein. Proc Natl Acad Sci U S A 93:11085–11090 [CrossRef]
     [Google Scholar]
  143. Kaye K. M., Izumi K. M., Li H., Johannsen E., Davidson D., Longnecker R., Kieff E. 1999; An Epstein-Barr virus that expresses only the first 231 LMP1 amino acids efficiently initiates primary B-lymphocyte growth transformation. J Virol 73:10525–10530
     [Google Scholar]
  144. Kaykas A., Worringer K., Sugden B. 2001; CD40 and LMP-1 both signal from lipid rafts but LMP-1 assembles a distinct, more efficient signaling complex. EMBO J 20:2641–2654 [CrossRef]
     [Google Scholar]
  145. Kieser A., Kilger E., Gires O., Ueffing M., Kolch W., Hammerschmidt W. 1997; Epstein–Barr virus latent membrane protein-1 triggers AP-1 activity via the c-Jun N-terminal kinase cascade. EMBO J 16:6478–6485 [CrossRef]
     [Google Scholar]
  146. Kieser A., Kaiser C., Hammerschmidt W. 1999; LMP1 signal transduction differs substantially from TNF receptor 1 signaling in the molecular functions of TRADD and TRAF2. EMBO J 18:2511–2521 [CrossRef]
     [Google Scholar]
  147. Kilger E., Kieser A., Baumann M., Hammerschmidt W. 1998; Epstein–Barr virus-mediated B-cell proliferation is dependent upon latent membrane protein 1, which simulates an activated CD40 receptor. EMBO J 17:1700–1709 [CrossRef]
     [Google Scholar]
  148. Kim O.-J., Yates J. L. 1993; Mutants of Epstein-Barr virus with a selective marker disrupting the TP gene transform B cells and replicate normally in culture. J Virol 67:7634–7640
     [Google Scholar]
  149. Kim K.-R., Yoshizaki T., Miyamori H., Hasegawa K., Horikawa T., Furukawa M., Harada S., Seiki M., Sato H. 2000; Transformation of Madin-Darby canine kidney (MDCK) epithelial cells by Epstein-Barr virus latent membrane protein 1 (LMP1) induces expression of Ets1 and invasive growth. Oncogene 19:1764–1771 [CrossRef]
     [Google Scholar]
  150. Kjellen P., Amdjadi K., Lund T. C., Medveczky P. G., Sefton B. M. 2002; The herpesvirus saimiri Tip484 and Tip488 proteins both stimulate Lck tyrosine protein kinase activity in vivo and in vitro . Virology 297:281–288 [CrossRef]
     [Google Scholar]
  151. Kretschmer C., Murphy C., Biesinger B., Beckers J., Fickenscher H., Kirchner T., Fleckenstein B., Ruther U. 1996; A Herpes saimiri oncogene causing peripheral T-cell lymphoma in transgenic mice. Oncogene 12:1609–1616
     [Google Scholar]
  152. Kube D., Holtick U., Vockerodt M., Ahmadi T., Haier B., Behrmann I., Heinrich P. C., Diehl V., Tesch H. 2001; STAT3 is constitutively activated in Hodgkin cell lines. Blood 98:762–770 [CrossRef]
     [Google Scholar]
  153. Kulwichit W., Edwards R. H., Davenport E. M., Baskar J. F., Godfrey V., Raab-Traub N. 1998; Expression of the Epstein-Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice. Proc Natl Acad Sci U S A 95:11963–11968 [CrossRef]
     [Google Scholar]
  154. Lacoste V., Judde J.-G., Briére J. & 11 other authors (2000a). Molecular epidemiology of human herpesvirus 8 in Africa: both B and A5 K1 genotypes, as well as the M and P genotypes of K14.1/K15 loci, are frequent and widespread. Virology 278:60–74 [CrossRef]
     [Google Scholar]
  155. Lacoste V., Mauclere P., Dubreuil G., Lewis J., Georges-Courbot M.-C., Gessain A. 2000b; KSHV-like herpesviruses in chimps and gorillas. Nature 407:151–152 [CrossRef]
     [Google Scholar]
  156. Lacoste V., Mauclere P., Dubreuil G., Lewis J., Georges-Courbot M.-C., Rigoulet J., Petit T., Gessain A. 2000c; Simian homologues of human gamma-2 and betaherpesviruses in mandrill and drill monkeys. J Virol 74:11993–11999 [CrossRef]
     [Google Scholar]
  157. Lagunoff M., Ganem D. 1997; The structure and coding organization of the genomic termini of Kaposi's sarcoma-associated herpesvirus. Virology 236:147–154 [CrossRef]
     [Google Scholar]
  158. Lagunoff M., Majeti R., Weiss A., Ganem D. 1999; Deregulated signal transduction by the K1 gene product of Kaposi's sarcoma-associated herpesvirus. Proc Natl Acad Sci U S A 96:5704–5709 [CrossRef]
     [Google Scholar]
  159. Lagunoff M., Lukac D. M., Ganem D. 2001; Immunoreceptor tyrosine-based activation motif-dependent signaling by Kaposi's sarcoma-associated herpesvirus K1 protein: effects on lytic viral replication. J Virol 75:5891–5898 [CrossRef]
     [Google Scholar]
  160. Laherty C. D., Hu H. M., Opipari A. W., Wang F., Dixit V. M. 1992; The Epstein-Barr virus LMP1 gene product induces A20 zinc finger protein expression by activating nuclear factor κ B. J Biol Chem 267:24157–24160
     [Google Scholar]
  161. Lam N., Sugden B. 2003; LMP1, a viral relative of the TNF receptor family, signals principally from intracellular compartments. EMBO J 22:3027–3038 [CrossRef]
     [Google Scholar]
  162. Laufs R., Melendez L. V. 1973; Oncogenicity of Herpesvirus ateles in monkeys. J Natl Cancer Inst 51:599–608
     [Google Scholar]
  163. Laux G., Perricaudet M., Farrell P. J. 1988; A spliced Epstein–Barr virus gene expressed in immortalized lymphocytes is created by circularization of the linear viral genome. EMBO J 7:769–774
     [Google Scholar]
  164. Laux G., Economou A., Farrell P. J. 1989; The terminal protein gene 2 of Epstein–Barr virus is transcribed from a bidirectional latent promoter region. J Gen Virol 70:3079–3084 [CrossRef]
     [Google Scholar]
  165. Lee H., Trimble J. J., Yoon D.-W., Regier D., Desrosiers R. C., Jung J. U. 1997; Genetic variation of herpesvirus saimiri subgroup A transforming protein and its association with cellular src. J Virol 71:3817–3825
     [Google Scholar]
  166. Lee H., Veazey R., Williams K. & 7 other authors (1998a). Deregulation of cell growth by the K1 gene of Kaposi's sarcoma-associated herpesvirus. Nat Med 4:435–440 [CrossRef]
     [Google Scholar]
  167. Lee H., Guo J., Li M., Choi J.-K., DeMaria M., Rosenzweig M., Jung J. U. 1998b; Identification of an immunoreceptor tyrosine-based activation motif of K1 transforming protein of Kaposi's sarcoma-associated herpesvirus. Mol Cell Biol 18:5219–5228
     [Google Scholar]
  168. Lee H., Choi J.-K., Li M., Kaye K., Kieff E., Jung J. U. 1999; Role of cellular tumor necrosis factor receptor-associated factors in NF- κ B activation and lymphocyte transformation by herpesvirus saimiri STP. J Virol 73:3913–3919
     [Google Scholar]
  169. Lee B.-S., Alvarez X., Ishido S., Lackner A. A., Jung J. U. 2000; Inhibition of intracellular transport of B cell antigen receptor complexes by Kaposi's sarcoma-associated herpesvirus K1. J Exp Med 192:11–21 [CrossRef]
     [Google Scholar]
  170. Lee B.-S., Paulose-Murphy M., Chung Y.-H., Connlole M., Zeichner S., Jung J. U. 2002; Suppression of tetradecanoyl phorbol acetate-induced lytic reactivation of Kaposi's sarcoma-associated herpesvirus by K1 signal transduction. J Virol 76:12185–12199 [CrossRef]
     [Google Scholar]
  171. Lee B.-S., Connole M., Tang Z., Harris N. L., Jung J. U. 2003; Structural analysis of the Kaposi's sarcoma-associated herpesvirus K1 protein. J Virol 77:8072–8086 [CrossRef]
     [Google Scholar]
  172. Lee B.-S., Lee S.-H., Feng P., Chang H., Cho N.-H., Jung J. U. 2005; Characterization of the Kaposi's sarcoma-associated herpesvirus K1 signalosome. J Virol 79:12173–12184 [CrossRef]
     [Google Scholar]
  173. Li S. N., Chang Y. S., Liu S. T. 1996; Effect of a 10-amino acid deletion on the oncogenic activity of latent membrane protein 1 of Epstein-Barr virus. Oncogene 12:2129–2135
     [Google Scholar]
  174. Liebowitz D., Wang D., Kieff E. 1986; Orientation and patching of the latent infection membrane protein encoded by Epstein-Barr virus. J Virol 58:233–237
     [Google Scholar]
  175. Liebowitz D., Kopan R., Fuchs E., Sample J., Kieff E. 1987; An Epstein-Barr virus transforming protein associates with vimentin in lymphocytes. Mol Cell Biol 7:2299–2308
     [Google Scholar]
  176. Liebowitz D., Mannick J., Takada K., Kieff E. 1992; Phenotypes of Epstein-Barr virus LMP1 deletion mutants indicate transmembrane and amino-terminal cytoplasmic domains necessary for effects in B-lymphoma cells. J Virol 66:4612–4616
     [Google Scholar]
  177. Liu L.-T., Peng J.-P., Chang H.-C., Hung W.-C. 2003; RECK is a target of Epstein–Barr virus latent membrane protein 1. Oncogene 22:8263–8270 [CrossRef]
     [Google Scholar]
  178. Liu M.-T., Chang Y.-T., Chen S.-C., Chuang Y.-C., Chen Y.-R., Lin C.-S., Chen J.-Y. 2005; Epstein–Barr virus latent membrane protein 1 represses p53-mediated DNA repair and transcriptional activity. Oncogene 24:2635–2646 [CrossRef]
     [Google Scholar]
  179. Longan L., Longnecker R. 2000; Epstein–Barr virus latent membrane protein 2A has no growth-altering effects when expressed in differentiating epithelia. J Gen Virol 81:2245–2252
     [Google Scholar]
  180. Longnecker R. 2000; Epstein-Barr virus latency: LMP2, a regulator or means for Epstein-Barr virus persistence?. Adv Cancer Res 79:175–200
     [Google Scholar]
  181. Longnecker R., Druker B., Roberts T. M., Kieff E. 1991; An Epstein-Barr virus protein associated with cell growth transformation interacts with a tyrosine kinase. J Virol 65:3681–3692
     [Google Scholar]
  182. Longnecker R., Miller C. L., Miao X.-Q., Marchini A., Kieff E. 1992; The only domain which distinguishes Epstein-Barr virus latent membrane protein 2A (LMP2A) from LMP2B is dispensable for lymphocyte infection and growth transformation in vitro; LMP2A is therefore nonessential. J Virol 66:6461–6469
     [Google Scholar]
  183. Longnecker R., Miller C. L., Tomkinson B., Miao X.-Q., Kieff E. 1993a; Deletion of DNA encoding the first five transmembrane domains of Epstein-Barr virus latent membrane proteins 2A and 2B. J Virol 67:5068–5074
     [Google Scholar]
  184. Longnecker R., Miller C. L., Miao X.-Q., Tomkinson B., Kieff E. 1993b; The last seven transmembrane and carboxy-terminal cytoplasmic domains of Epstein-Barr virus latent membrane protein 2 (LMP2) are dispensable for lymphocyte infection and growth transformation in vitro. J Virol 67:2006–2013
     [Google Scholar]
  185. Longnecker R., Merchant M., Brown M. E., Fruehling S., Bickford J. O., Ikeda M., Harty R. N. 2000; WW- and SH3-domain interactions with Epstein-Barr virus LMP2A. Exp Cell Res 257:332–340 [CrossRef]
     [Google Scholar]
  186. Luftig M., Prinarakis E., Yasui T. & 12 other authors 2003; Epstein–Barr virus latent membrane protein 1 activation of NF- κ B through IRAK1 and TRAF6. Proc Natl Acad Sci U S A 100:15595–15600 [CrossRef]
     [Google Scholar]
  187. Luftig M., Yasui T., Soni V., Kang M.-S., Jacobson N., Cahir-McFarland E., Seed B., Kieff E. 2004; Epstein–Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKK α -dependent noncanonical NF- κ B activation. Proc Natl Acad Sci U S A 101:141–146 [CrossRef]
     [Google Scholar]
  188. Lund T., Medveczky M. M., Geck P., Medveczky P. G. 1995; A herpesvirus saimiri protein required for interleukin-2 independence is associated with membranes of transformed T cells. J Virol 69:4495–4499
     [Google Scholar]
  189. Lund T., Medveczky M. M., Neame P. J., Medveczky P. G. 1996; A herpesvirus saimiri membrane protein required for interleukin-2 independence forms a stable complex with p56 lck . J Virol 70:600–606
     [Google Scholar]
  190. Lund T., Medveczky M. M., Medveczky P. G. 1997a; Herpesvirus saimiri Tip-484 membrane protein markedly increases p56 lck activity in T cells. J Virol 71:378–382
     [Google Scholar]
  191. Lund T. C., Garcia R., Medveczky M. M., Jove R., Medveczky P. G. 1997b; Activation of STAT transcription factors by herpesvirus Saimiri Tip-484 requires p56 lck . J Virol 71:6677–6682
     [Google Scholar]
  192. Lund T. C., Prator P. C., Medveczky M. M., Medveczky P. G. 1999; The Lck binding domain of herpesvirus saimiri Tip-484 constitutively activates Lck and STAT3 in T cells. J Virol 73:1689–1694
     [Google Scholar]
  193. Mainou B. A., Everly D. N. Jr, Raab-Traub N. 2005; Epstein–Barr virus latent membrane protein 1 CTAR1 mediates rodent and human fibroblast transformation through activation of PI3K. Oncogene 24:6917–6924 [CrossRef]
     [Google Scholar]
  194. Mancao C., Altmann M., Jungnickel B., Hammerschmidt W. 2005; Rescue of “crippled” germinal center B cells from apoptosis by Epstein-Barr virus. Blood 106:4339–4344 [CrossRef]
     [Google Scholar]
  195. Mann K. P., Thorley-Lawson D. 1987; Posttranslational processing of the Epstein-Barr virus-encoded p63/LMP protein. J Virol 61:2100–2108
     [Google Scholar]
  196. Mansfield K. G., Westmoreland S. V., DeBakker C. D., Czajak S., Lackner A. A., Desrosiers R. C. 1999; Experimental infection of rhesus and pig-tailed macaques with macaque rhadinoviruses. J Virol 73:10320–10328
     [Google Scholar]
  197. Martin J., Sugden B. 1991; Transformation by the oncogenic latent membrane protein correlates with its rapid turnover, membrane localization, and cytoskeletal association. J Virol 65:3246–3258
     [Google Scholar]
  198. Martin J. M., Veis D., Korsmeyer S. J., Sugden B. 1993; Latent membrane protein of Epstein-Barr virus induces cellular phenotypes independently of expression of Bcl-2. J Virol 67:5269–5278
     [Google Scholar]
  199. Massagué J., Wotton D. 2000; Transcriptional control by the TGF- β /Smad signaling system. EMBO J 19:1745–1754 [CrossRef]
     [Google Scholar]
  200. McGeoch D. J., Gatherer D., Dolan A. 2005; On phylogenetic relationships among major lineages of the Gammaherpesvirinae . J Gen Virol 86:307–316 [CrossRef]
     [Google Scholar]
  201. Medveczky P., Szomolanyi E., Desrosiers R. C., Mulder C. 1984; Classification of herpesvirus saimiri into three groups based on extreme variation in a DNA region required for oncogenicity. J Virol 52:938–944
     [Google Scholar]
  202. Medveczky M. M., Szomolanyi E., Hesselton R., DeGrand D., Geck P., Medveczky P. G. 1989; Herpesvirus saimiri strains from three DNA subgroups have different oncogenic potentials in New Zealand white rabbits. J Virol 63:3601–3611
     [Google Scholar]
  203. Medveczky M. M., Geck P., Vassallo R., Medveczky P. G. 1993a; Expression of the collagen-like putative oncoprotein of Herpesvirus saimiri in transformed T cells. Virus Genes 7:349–365 [CrossRef]
     [Google Scholar]
  204. Medveczky M. M., Geck P., Sullivan J. L., Serbousek D., Djeu J. Y., Medveczky P. G. 1993b; IL-2 independent growth and cytotoxicity of herpesvirus saimiri-infected human CD8 cells and involvement of two open reading frame sequences of the virus. Virology 196:402–412 [CrossRef]
     [Google Scholar]
  205. Mehl A. M., Fischer N., Rowe M., Hartmann F., Daus H., Trümper L., Pfreundschuh M., Müller-Lantzsch N., Grässer F. A. 1998; Isolation and analysis of two strongly transforming isoforms of the Epstein-Barr-virus(EBV)-encoded latent membrane protein-1 (LMP1) from a single Hodgkin's lymphoma. Int J Cancer 76:194–200 [CrossRef]
     [Google Scholar]
  206. Mehl A. M., Floettmann J. E., Jones M., Brennan P., Rowe M. 2001; Characterization of intercellular adhesion molecule-1 regulation by Epstein-Barr virus-encoded latent membrane protein-1 identifies pathways that cooperate with nuclear factor κ B to activate transcription. J Biol Chem 276:984–992 [CrossRef]
     [Google Scholar]
  207. Melendez L. V., Daniel M. D., Hunt R. D., Garcia F. G. 1968; An apparently new herpesvirus from primary kidney cultures of the squirrel monkey ( Saimiri sciureus ). Lab Anim Care 18:374–381
     [Google Scholar]
  208. Melendez L. V., Daniel M. D., Garcia F. G., Fraser C. E., Hunt R. D., King N. W. 1969a; Herpesvirus saimiri. I. Further characterization studies of a new virus from the squirrel monkey. Lab Anim Care 19:372–377
     [Google Scholar]
  209. Melendez L. V., Hunt R. D., Daniel M. D., Garcia F. G., Fraser C. E. 1969b; Herpesvirus saimiri. II. Experimentally induced malignant lymphoma in primates. Lab Anim Care 19:378–386
     [Google Scholar]
  210. Melendez L. V., Hunt R. D., King N. W., Barahona H. H., Daniel M. D., Fraser C. E., Garcia F. G. 1972a; Herpesvirus ateles, a new lymphoma virus of monkeys. Nat New Biol 235:182–184
     [Google Scholar]
  211. Melendez L. V., Hunt R. D., Daniel M. D., Fraser C. E., Barahona H. H., King N. W., Garcia F. G. 1972b; Herpesviruses saimiri and ateles – their role in malignant lymphomas of monkeys. Fed Proc 31:1643–1650
     [Google Scholar]
  212. Melendez L. V., Castellanos H., Barahona H. H., Daniel M. D., Hunt R. D., Fraser C. E., Garcia F. G., King N. W. 1972c; Two new herpesviruses from spider monkeys ( Ateles geoffroyi ). J Natl Cancer Inst 49:233–238
     [Google Scholar]
  213. Melendez L. V., Hunt R. D., Garcia F. G., Daniel M. D., Fraser C. E., Barahona H. H., King N. W. 1973; Herpesvirus ateles, the second lymphoma virus of monkeys. Bibl Haematol 39:410–415
     [Google Scholar]
  214. Merchant M., Caldwell R. G., Longnecker R. 2000; The LMP2A ITAM is essential for providing B cells with development and survival signals in vivo. J Virol 74:9115–9124 [CrossRef]
     [Google Scholar]
  215. Merlo J. J., Tsygankov A. Y. 2001; Herpesvirus saimiri oncoproteins Tip and StpC synergistically stimulate NF- κ B activity and interleukin-2 gene expression. Virology 279:325–338 [CrossRef]
     [Google Scholar]
  216. Miller C. L., Longnecker R., Kieff E. 1993; Epstein-Barr virus latent membrane protein 2A blocks calcium mobilization in B lymphocytes. J Virol 67:3087–3094
     [Google Scholar]
  217. Miller C. L., Lee J. H., Kieff E., Longnecker R. 1994a; An integral membrane protein (LMP2) blocks reactivation of Epstein–Barr virus from latency following surface immunoglobulin crosslinking. Proc Natl Acad Sci U S A 91:772–776 [CrossRef]
     [Google Scholar]
  218. Miller C. L., Lee J. H., Kieff E., Burkhardt A. L., Bolen J. B., Longnecker R. 1994b; Epstein-Barr virus protein LMP2A regulates reactivation from latency by negatively regulating tyrosine kinases involved in sIg-mediated signal transduction. Infect Agents Dis 3:128–136
     [Google Scholar]
  219. Miller W. E., Earp H. S., Raab-Traub N. 1995a; The Epstein-Barr virus latent membrane protein 1 induces expression of the epidermal growth factor receptor. J Virol 69:4390–4398
     [Google Scholar]
  220. Miller C. L., Burkhardt A. L., Lee J. H., Stealey B., Longnecker R., Bolen J. B., Kieff E. 1995b; Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases. Immunity 2:155–166 [CrossRef]
     [Google Scholar]
  221. Miller W. E., Mosialos G., Kieff E., Raab-Traub N. 1997; Epstein-Barr virus LMP1 induction of the epidermal growth factor receptor is mediated through a TRAF signaling pathway distinct from NF- κ B activation. J Virol 71:586–594
     [Google Scholar]
  222. Milner A. E., Johnson G. D., Gregory C. D. 1992; Prevention of programmed cell death in Burkitt lymphoma cell lines by bcl-2-dependent and -independent mechanisms. Int J Cancer 52:636–644 [CrossRef]
     [Google Scholar]
  223. Mitchell T., Sugden B. 1995; Stimulation of NF-kappa B-mediated transcription by mutant derivatives of the latent membrane protein of Epstein-Barr virus. J Virol 69:2968–2976
     [Google Scholar]
  224. Moody C. A., Scott R. S., Amirghahari N., Nathan C.-A., Young L. S., Dawson C. W., Sixbey J. W. 2005; Modulation of the cell growth regulator mTOR by Epstein-Barr virus-encoded LMP2A. J Virol 79:5499–5506 [CrossRef]
     [Google Scholar]
  225. Moorthy R., Thorley-Lawson D. A. 1990; Processing of the Epstein-Barr virus-encoded latent membrane protein p63/LMP. J Virol 64:829–837
     [Google Scholar]
  226. Moorthy R. K., Thorley-Lawson D. A. 1993a; All three domains of the Epstein-Barr virus-encoded latent membrane protein LMP-1 are required for transformation of rat-1 fibroblasts. J Virol 67:1638–1646
     [Google Scholar]
  227. Moorthy R. K., Thorley-Lawson D. A. 1993b; Biochemical, genetic, and functional analyses of the phosphorylation sites on the Epstein-Barr virus-encoded oncogenic latent membrane protein LMP-1. J Virol 67:2637–2645
     [Google Scholar]
  228. Morrison J. A., Raab-Traub N. 2005; Roles of the ITAM and PY motifs of Epstein-Barr virus latent membrane protein 2A in the inhibition of epithelial cell differentiation and activation of β -catenin signaling. J Virol 79:2375–2382 [CrossRef]
     [Google Scholar]
  229. Morrison J. A., Klingelhutz A. J., Raab-Traub N. 2003; Epstein-Barr virus latent membrane protein 2A activates β -catenin signaling in epithelial cells. J Virol 77:12276–12284 [CrossRef]
     [Google Scholar]
  230. Mosialos G., Birkenbach M., Yalamanchili R., Van Arsdale T., Ware C., Kieff E. 1995; The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell 80:389–399 [CrossRef]
     [Google Scholar]
  231. Murono S., Inoue H., Tanabe T., Joab I., Yoshizaki T., Furukawa M., Pagano J. S. 2001; Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells. Proc Natl Acad Sci U S A 98:6905–6910 [CrossRef]
     [Google Scholar]
  232. Murphy C., Kretschmer C., Biesinger B., Beckers J., Jung J., Desrosiers R. C., Muller-Hermelink H. K., Fleckenstein B. W., Ruther U. 1994; Epithelial tumours induced by a herpesvirus oncogene in transgenic mice. Oncogene 9:221–226
     [Google Scholar]
  233. Murthy S. C. S., Trimble J. J., Desrosiers R. C. 1989; Deletion mutants of herpesvirus saimiri define an open reading frame necessary for transformation. J Virol 63:3307–3314
     [Google Scholar]
  234. Najjar I., Baran-Marszak F., Le Clorennec C. & 8 other authors 2005; Latent membrane protein 1 regulates STAT1 through NF- κ B-dependent interferon secretion in Epstein-Barr virus-immortalized B cells. J Virol 79:4936–4943 [CrossRef]
     [Google Scholar]
  235. Nakamura H., Lu M., Gwack Y., Souvlis J., Zeichner S. L., Jung J. U. 2003; Global changes in Kaposi's sarcoma-associated virus gene expression patterns following expression of a tetracycline-inducible Rta transactivator. J Virol 77:4205–4220 [CrossRef]
     [Google Scholar]
  236. Nicholas J., Zong J. C., Alcendor D. J. & 9 other authors 1998; Novel organizational features, captured cellular genes, and strain variability within the genome of KSHV/HHV8. J Natl Cancer Inst Monogr 23:79–88
     [Google Scholar]
  237. Ohtani N., Zebedee Z., Huot T. J. G., Stinson J. A., Sugimoto M., Ohashi Y., Sharrocks A. D., Peters G., Hara E. 2001; Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence. Nature 409:1067–1070 [CrossRef]
     [Google Scholar]
  238. Ohtani N., Brennan P., Gaubatz S., Sanij E., Hertzog P., Wolvetang E., Ghysdael J., Rowe M., Hara E. 2003; Epstein-Barr virus LMP1 blocks p16INK4a–RB pathway by promoting nuclear export of E2F4/5. J Cell Biol 162:173–183 [CrossRef]
     [Google Scholar]
  239. Panousis C. G., Rowe D. T. 1997; Epstein-Barr virus latent membrane protein 2 associates with and is a substrate for mitogen-activated protein kinase. J Virol 71:4752–4760
     [Google Scholar]
  240. Park J., Lee B.-S., Choi J.-K., Means R. E., Choe J., Jung J. U. 2002; Herpesviral protein targets a cellular WD repeat endosomal protein to downregulate T lymphocyte receptor expression. Immunity 17:221–233 [CrossRef]
     [Google Scholar]
  241. Park J., Cho N.-H., Choi J.-K., Feng P., Choe J., Jung J. U. 2003; Distinct roles of cellular Lck and p80 proteins in herpesvirus saimiri Tip function on lipid rafts. J Virol 77:9041–9051 [CrossRef]
     [Google Scholar]
  242. Park J., Seo T., Jung J., Choe J. 2004; Herpesvirus saimiri STP A11 protein interacts with STAT3 and stimulates its transcriptional activity. Biochem Biophys Res Commun 320:279–285 [CrossRef]
     [Google Scholar]
  243. Pawson T., Gish G. D. 1992; SH2 and SH3 domains: from structure to function. Cell 71:359–362 [CrossRef]
     [Google Scholar]
  244. Peng M., Lundgren E. 1992; Transient expression of the Epstein-Barr virus LMP1 gene in human primary B cells induces cellular activation and DNA synthesis. Oncogene 7:1775–1782
     [Google Scholar]
  245. Peng M., Lundgren E. 1993; Transient expression of the Epstein-Barr virus LMP1 gene in B-cell chronic lymphocytic leukemia cells, T cells, and hematopoietic cell lines: cell-type-independent-induction of CD23, CD21, and ICAM-1. Leukemia 7:104–112
     [Google Scholar]
  246. Peng-Pilon M., Ruuth K., Lundgren E., Brodin P. 1995; The cytoplasmic C-terminal domain but not the N-terminal domain of latent membrane protein 1 of Epstein–Barr virus is essential for B cell activation. J Gen Virol 76:767–777 [CrossRef]
     [Google Scholar]
  247. Pomerantz J. L., Baltimore D. 2002; Two pathways to NF- κ B. Mol Cell 10:693–695 [CrossRef]
     [Google Scholar]
  248. Poole L. J., Zong J.-C., Ciufo D. M., Alcendor D. J., Cannon J. S., Ambinder R., Orenstein J. M., Reitz M. S., Hayward G. S. 1999; Comparison of genetic variability at multiple loci across the genomes of the major subtypes of Kaposi's sarcoma-associated herpesvirus reveals evidence for recombination and for two distinct types of open reading frame K15 alleles at the right-hand end. J Virol 73:6646–6660
     [Google Scholar]
  249. Portis T., Longnecker R. 2003; Epstein-Barr virus LMP2A interferes with global transcription factor regulation when expressed during B-lymphocyte development. J Virol 77:105–114 [CrossRef]
     [Google Scholar]
  250. Portis T., Longnecker R. 2004a; Epstein–Barr virus (EBV) LMP2A alters normal transcriptional regulation following B-cell receptor activation. Virology 318:524–533 [CrossRef]
     [Google Scholar]
  251. Portis T., Longnecker R. 2004b; Epstein–Barr virus (EBV) LMP2A mediates B-lymphocyte survival through constitutive activation of the Ras/PI3K/Akt pathway. Oncogene 23:8619–8628 [CrossRef]
     [Google Scholar]
  252. Portis T., Dyck P., Longnecker R. 2003; Epstein-Barr Virus (EBV) LMP2A induces alterations in gene transcription similar to those observed in Reed-Sternberg cells of Hodgkin lymphoma. Blood 102:4166–4178 [CrossRef]
     [Google Scholar]
  253. Portis T., Ikeda M., Longnecker R. 2004; Epstein-Barr virus LMP2A: regulating cellular ubiquitination processes for maintenance of viral latency?. Trends Immunol 25:422–426 [CrossRef]
     [Google Scholar]
  254. Prakash O., Tang Z.-Y., Peng X., Coleman R., Gill J., Farr G., Samaniego F. 2002; Tumorigenesis and aberrant signaling in transgenic mice expressing the human herpesvirus-8 K1 gene. J Natl Cancer Inst 94:926–935 [CrossRef]
     [Google Scholar]
  255. Prakash O., Swamy O. R., Peng X. & 8 other authors 2005; Activation of Src kinase Lyn by the Kaposi sarcoma-associated herpesvirus K1 protein: implications for lymphomagenesis. Blood 105:3987–3994 [CrossRef]
     [Google Scholar]
  256. Prokova V., Mosialos G., Kardassis D. 2002; Inhibition of transforming growth factor β signaling and Smad-dependent activation of transcription by the latent membrane protein 1 of Epstein-Barr virus. J Biol Chem 277:9342–9350 [CrossRef]
     [Google Scholar]
  257. Puls A., Eliopoulos A. G., Nobes C. D., Bridges T., Young L. S., Hall A. 1999; Activation of the small GTPase Cdc42 by the inflammatory cytokines TNF α and IL-1, and by the Epstein-Barr virus transforming protein LMP1. J Cell Sci 112:2983–2992
     [Google Scholar]
  258. Rickinson A. B., Kieff E. 2001; Epstein-Barr virus. In Fields Virology , 4th edn. pp  2575–2627 Edited by Knipe D. M., Howley P. M., Griffin D. E., Lamb R. A., Martin M. A., Roizman B., Straus S. E. Philadelphia, PA: Lippincott Williams & Wilkins;
     [Google Scholar]
  259. Rochford R., Miller C. L., Cannon M. J., Izumi K. M., Kieff E., Longnecker R. 1997; In vivo growth of Epstein-Barr virus transformed B cells with mutations in latent membrane protein 2 (LMP2). Arch Virol 142:707–720 [CrossRef]
     [Google Scholar]
  260. Rose T. M., Strand K. B., Schultz E. R., Schaefer G., Rankin G. W. Jr, Thouless M. E., Tsai C.-C., Bosch M. L. 1997; Identification of two homologs of the Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in retroperitoneal fibromatosis of different macaque species. J Virol 71:4138–4144
     [Google Scholar]
  261. Rowe M., Peng-Pilon M., Huen D. S., Hardy R., Croom-Carter D., Lundgren E., Rickinson A. B. 1994; Upregulation of bcl-2 by the Epstein-Barr virus latent membrane protein LMP1: a B-cell-specific response that is delayed relative to NF- κ B activation and to induction of cell surface markers. J Virol 68:5602–5612
     [Google Scholar]
  262. Russo J. J., Bohenzky R. A., Chien M.-C. & 8 other authors 1996; Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci U S A 93:14862–14867 [CrossRef]
     [Google Scholar]
  263. Saito N., Courtois G., Chiba A., Yamamoto N., Nitta T., Hironaka N., Rowe M., Yamamoto N., Yamaoka S. 2003; Two carboxyl-terminal activation regions of Epstein-Barr virus latent membrane protein 1 activate NF- κ B through distinct signaling pathways in fibroblast cell lines. J Biol Chem 278:46565–46575 [CrossRef]
     [Google Scholar]
  264. Samaniego F., Markham P. D., Gallo R. C., Ensoli B. 1995; Inflammatory cytokines induce AIDS-Kaposi's sarcoma-derived spindle cells to produce and release basic fibroblast growth factor and enhance Kaposi's sarcoma-like lesion formation in nude mice. J Immunol 154:3582–3592
     [Google Scholar]
  265. Samaniego F., Pati S., Karp J. E., Prakash O., Bose D. 2001; Human herpesvirus 8 K1-associated nuclear factor- κ B-dependent promoter activity: role in Kaposi's sarcoma inflammation?. J Natl Cancer Inst Monogr 28:15–23
     [Google Scholar]
  266. Sample J., Liebowitz D., Kieff E. 1989; Two related Epstein-Barr virus membrane proteins are encoded by separate genes. J Virol 63:933–937
     [Google Scholar]
  267. Sandberg M., Hammerschmidt W., Sugden B. 1997; Characterization of LMP-1's association with TRAF1, TRAF2, and TRAF3. J Virol 71:4649–4656
     [Google Scholar]
  268. Schaadt E., Baier B., Mautner J., Bornkamm G. W., Adler B. 2005; Epstein–Barr virus latent membrane protein 2A mimics B-cell receptor-dependent virus reactivation. J Gen Virol 86:551–559 [CrossRef]
     [Google Scholar]
  269. Scholle F., Longnecker R., Raab-Traub N. 1999; Epithelial cell adhesion to extracellular matrix proteins induces tyrosine phosphorylation of the Epstein-Barr virus latent membrane protein 2: a role for C-terminal Src kinase. J Virol 73:4767–4775
     [Google Scholar]
  270. Scholle F., Bendt K. M., Raab-Traub N. 2000; Epstein-Barr virus LMP2A transforms epithelial cells, inhibits cell differentiation, and activates Akt. J Virol 74:10681–10689 [CrossRef]
     [Google Scholar]
  271. Scholle F., Longnecker R., Raab-Traub N. 2001; Analysis of the phosphorylation status of Epstein–Barr virus LMP2A in epithelial cells. Virology 291:208–214 [CrossRef]
     [Google Scholar]
  272. Schultheiss U., Püschner S., Kremmer E., Mak T. W., Engelmann H., Hammerschmidt W., Kieser A. 2001; TRAF6 is a critical mediator of signal transduction by the viral oncogene latent membrane protein 1. EMBO J 20:5678–5691 [CrossRef]
     [Google Scholar]
  273. Schulz T. F. 2000; Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8): epidemiology and pathogenesis. J Antimicrob Chemother 45:15–27
     [Google Scholar]
  274. Schulz T. F. 2006; The pleiotropic effects of Kaposi's sarcoma-associated herpesvirus. J Pathol 208:187–198 [CrossRef]
     [Google Scholar]
  275. Schweimer K., Hoffmann S., Bauer F., Friedrich U., Kardinal C., Feller S. M., Biesinger B., Sticht H. 2002; Structural investigation of the binding of a herpesviral protein to the SH3 domain of tyrosine kinase Lck. Biochemistry 41:5120–5130 [CrossRef]
     [Google Scholar]
  276. Searles R. P., Bergquam E. P., Axthelm M. K., Wong S. W. 1999; Sequence and genomic analysis of a Rhesus macaque rhadinovirus with similarity to Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8. J Virol 73:3040–3053
     [Google Scholar]
  277. Sharp T. V., Wang H.-W., Koumi A., Hollyman D., Endo Y., Ye H., Du M.-Q., Boshoff C. 2002; K15 protein of Kaposi's sarcoma-associated herpesvirus is latently expressed and binds to HAX-1, a protein with antiapoptotic function. J Virol 76:802–816 [CrossRef]
     [Google Scholar]
  278. Song X., Tao Y.-G., Deng X.-Y., Jin X., Tan Y.-N., Tang M., Wu Q., Lee L. M., Cao Y. 2004; Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein–Barr virus encoded latent membrane protein 1. Cell Signal 16:1153–1162 [CrossRef]
     [Google Scholar]
  279. Song X., Tao Y. G., Zeng L., Deng X. Y., Lee L. M., Gong J. P., Wu Q., Cao Y. 2005; Latent membrane protein 1 encoded by Epstein-Barr virus modulates directly and synchronously cyclin D1 and p16 by newly forming a c-Jun/Jun B heterodimer in nasopharyngeal carcinoma cell line. Virus Res 113:89–99 [CrossRef]
     [Google Scholar]
  280. Songyang Z., Shoelson S. E., Chaudhuri M. & 14 other authors 1993; SH2 domains recognize specific phosphopeptide sequences. Cell 72:767–778 [CrossRef]
     [Google Scholar]
  281. Songyang Z., Blechner S., Hoagland N., Hoekstra M. F., Piwnica-Worms H., Cantley L. C. 1994a; Use of an oriented peptide library to determine the optimal substrates of protein kinases. Curr Biol 4:973–982 [CrossRef]
     [Google Scholar]
  282. Songyang Z., Shoelson S. E., McGlade J. & 12 other authors (1994b). Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav. Mol Cell Biol 14:2777–2785 [CrossRef]
     [Google Scholar]
  283. Sorokina E. M., Merlo J. J. Jr, Tsygankov A. Y. 2004; Molecular mechanisms of the effect of Herpesvirus saimiri protein StpC on the signaling pathway leading to NF- κ B activation. J Biol Chem 279:13469–13477 [CrossRef]
     [Google Scholar]
  284. Speck P., Kline K. A., Cheresh P., Longnecker R. 1999; Epstein–Barr virus lacking latent membrane protein 2 immortalizes B cells with efficiency indistinguishable from that of wild-type virus. J Gen Virol 80:2193–2203
     [Google Scholar]
  285. Sudol M. 1996; Structure and function of the WW domain. Prog Biophys Mol Biol 65:113–132
     [Google Scholar]
  286. Swart R., Ruf I. K., Sample J., Longnecker R. 2000; Latent membrane protein 2A-mediated effects on the phosphatidylinositol 3-kinase/Akt pathway. J Virol 74:10838–10845 [CrossRef]
     [Google Scholar]
  287. Szomolanyi E., Medveczky P., Mulder C. 1987; In vitro immortalization of marmoset cells with three subgroups of herpesvirus saimiri. J Virol 61:3485–3490
     [Google Scholar]
  288. Tao Y. G., Tan Y. N., Liu Y. P. & 7 other authors 2004; Epstein-Barr virus latent membrane protein 1 modulates epidermal growth factor receptor promoter activity in a nuclear factor kappa B-dependent manner. Cell Signal 16:781–790 [CrossRef]
     [Google Scholar]
  289. Tao Y., Song X., Deng X. & 9 other authors 2005; Nuclear accumulation of epidermal growth factor receptor and acceleration of G1/S stage by Epstein–Barr-encoded oncoprotein latent membrane protein 1. Exp Cell Res 303:240–251 [CrossRef]
     [Google Scholar]
  290. Thorley-Lawson D. A. 2001; Epstein-Barr virus: exploiting the immune system. Nat Rev Immunol 1:75–82 [CrossRef]
     [Google Scholar]
  291. Tomlinson C. C., Damania B. 2004; The K1 protein of Kaposi's sarcoma-associated herpesvirus activates the Akt signaling pathway. J Virol 78:1918–1927 [CrossRef]
     [Google Scholar]
  292. Tsai C.-N., Tsai C.-L., Tse K.-P., Chang H.-Y., Chang Y.-S. 2002; The Epstein-Barr virus oncogene product, latent membrane protein 1, induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases. Proc Natl Acad Sci U S A 99:10084–10089 [CrossRef]
     [Google Scholar]
  293. Uchida J., Yasui T., Takaoka-Shichijo Y., Muraoka M., Kulwichit W., Raab-Traub N., Kikutani H. 1999; Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses. Science 286:300–303 [CrossRef]
     [Google Scholar]
  294. Vazirabadi G., Geiger T. R., Coffin W. F. III, Martin J. M. 2003; Epstein–Barr virus latent membrane protein-1 (LMP-1) and lytic LMP-1 localization in plasma membrane-derived extracellular vesicles and intracellular virions. J Gen Virol 84:1997–2008 [CrossRef]
     [Google Scholar]
  295. Vockerodt M., Haier B., Buttgereit P., Tesch H., Kube D. 2001; The Epstein–Barr virus latent membrane protein 1 induces interleukin-10 in Burkitt's lymphoma cells but not in Hodgkin's cells involving the p38/SAPK2 pathway. Virology 280:183–198 [CrossRef]
     [Google Scholar]
  296. Vockerodt M., Pinkert D., Smola-Hess S., Michels A., Ransohoff R. M., Tesch H., Kube D. 2005; The Epstein-Barr virus oncoprotein latent membrane protein 1 induces expression of the chemokine IP-10: importance of mRNA half-life regulation. Int J Cancer 114:598–605 [CrossRef]
     [Google Scholar]
  297. Wan J., Sun L., Mendoza J. W. & 10 other authors 2004; Elucidation of the c-Jun N-terminal kinase pathway mediated by Estein-Barr virus-encoded latent membrane protein 1. Mol Cell Biol 24:192–199 [CrossRef]
     [Google Scholar]
  298. Wang D., Liebowitz D., Kieff E. 1985; An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell 43:831–840 [CrossRef]
     [Google Scholar]
  299. Wang D., Liebowitz D., Wang F., Gregory C., Rickinson A., Larson R., Springer T., Kieff E. 1988a; Epstein-Barr virus latent infection membrane protein alters the human B-lymphocyte phenotype: deletion of the amino terminus abolishes activity. J Virol 62:4173–4184
     [Google Scholar]
  300. Wang D., Liebowitz D., Kieff E. 1988b; The truncated form of the Epstein-Barr virus latent-infection membrane protein expressed in virus replication does not transform rodent fibroblasts. J Virol 62:2337–2346
     [Google Scholar]
  301. Wang F., Gregory C., Sample C., Rowe M., Liebowitz D., Murray R., Rickinson A., Kieff E. 1990; Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J Virol 64:2309–2318
     [Google Scholar]
  302. Wang S., Rowe M., Lundgren E. 1996; Expression of the Epstein Barr virus transforming protein LMP1 causes a rapid and transient stimulation of the Bcl-2 homologue Mcl-1 levels in B-cell lines. Cancer Res 56:4610–4613
     [Google Scholar]
  303. Wang L., Wakisaka N., Tomlinson C. C., DeWire S. M., Krall S., Pagano J. S., Damania B. 2004; The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) K1 protein induces expression of angiogenic and invasion factors. Cancer Res 64:2774–2781 [CrossRef]
     [Google Scholar]
  304. Weber-Nordt R. M., Egen C., Wehinger J., Ludwig W., Gouilleux-Gruart V., Mertelsmann R., Finke J. 1996; Constitutive activation of STAT proteins in primary lymphoid and myeloid leukemia cells and in Epstein-Barr virus (EBV)-related lymphoma cell lines. Blood 88:809–816
     [Google Scholar]
  305. Wehner L.-E., Schröder N., Kamino K., Friedrich U., Biesinger B., Rüther U. 2001; Herpesvirus saimiri Tip gene causes T-cell lymphomas in transgenic mice. DNA Cell Biol 20:81–88 [CrossRef]
     [Google Scholar]
  306. Wiese N., Tsygankov A. Y., Klauenberg U., Bolen J. B., Fleischer B., Bröker B. M. 1996; Selective activation of T cell kinase p56 lck by Herpesvirus saimiri protein tip. J Biol Chem 271:847–852 [CrossRef]
     [Google Scholar]
  307. Wilson J. B., Weinberg W., Johnson R., Yuspa S., Levine A. J. 1990; Expression of the BNLF-1 oncogene of Epstein-Barr virus in the skin of transgenic mice induces hyperplasia and aberrant expression of keratin 6. Cell 61:1315–1327 [CrossRef]
     [Google Scholar]
  308. Winberg G., Matskova L., Chen F., Plant P., Rotin D., Gish G., Ingham R., Ernberg I., Pawson T. 2000; Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3 protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases. Mol Cell Biol 20:8526–8535 [CrossRef]
     [Google Scholar]
  309. Wong S. W., Bergquam E. P., Swanson R. M., Lee F. W., Shiigi S. M., Avery N. A., Fanton J. W., Axthelm M. K. 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 190:827–840 [CrossRef]
     [Google Scholar]
  310. Xie P., Bishop G. A. 2004; Roles of TNF receptor-associated factor 3 in signaling to B lymphocytes by carboxyl-terminal activating regions 1 and 2 of the EBV-encoded oncoprotein latent membrane protein 1. J Immunol 173:5546–5555 [CrossRef]
     [Google Scholar]
  311. Xie P., Hostager B. S., Bishop G. A. 2004; Requirement for TRAF3 in signaling by LMP1 but not CD40 in B lymphocytes. J Exp Med 199:661–671 [CrossRef]
     [Google Scholar]
  312. Xin B., He Z., Yang X., Chan C.-P., Ng M.-H., Cao L. 2001; TRADD domain of Epstein-Barr virus transforming protein LMP1 is essential for inducing immortalization and suppressing senescence of primary rodent fibroblasts. J Virol 75:3010–3015 [CrossRef]
     [Google Scholar]
  313. Yang X., He Z., Xin B., Cao L. 2000; LMP1 of Epstein–Barr virus suppresses cellular senescence associated with the inhibition of p16INK4a expression. Oncogene 19:2002–2013 [CrossRef]
     [Google Scholar]
  314. Yasui T., Luftig M., Soni V., Kieff E. 2004; Latent infection membrane protein transmembrane FWLY is critical for intermolecular interaction, raft localization, and signaling. Proc Natl Acad Sci U S A 101:278–283 [CrossRef]
     [Google Scholar]
  315. Yoon D. W., Lee H., Seol W., DeMaria M., Rosenzweig M., Jung J. U. 1997; Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation. Immunity 6:571–582 [CrossRef]
     [Google Scholar]
  316. Zhang L., Wu L., Hong K., Pagano J. S. 2001; Intracellular signaling molecules activated by Epstein-Barr virus for induction of interferon regulatory factor 7. J Virol 75:12393–12401 [CrossRef]
     [Google Scholar]
  317. Zong J.-C., Ciufo D. M., Alcendor D. J. & 14 other authors 1999; High-level variability in the ORF-K1 membrane protein gene at the left end of the Kaposi's sarcoma-associated herpesvirus genome defines four major virus subtypes and multiple variants or clades in different human populations. J Virol 73:4156–4170
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81598-0
Loading
Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae
J. Gen. Virol. 87, 1047 (2006); https://doi.org/10.1099/vir.0.81598-0
/content/journal/jgv/10.1099/vir.0.81598-0
/content/journal/jgv/10.1099/vir.0.81598-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error