Skip to main content
SpringerLink
Log in

Epstein-Barr Virus

Mechanisms of Oncogenesis

  • Chapter
DNA Tumor Viruses

Part of the book series: Infectious Agents and Pathogenesis ((IAPA))

Abstract

Epstein-Barr virus (EBV), like all human herpesviruses, infects almost all of the world’s population with an asymptomatic or trivial primary infection followed by lifelong persistence. Despite the ubiquitous nature of EBV and its potent in vitro immortalizing ability, the persistent infection is only rarely associated with disease. However, when the balance between the virus and the cell, and/or the infected cell and the immune system, is disturbed, serious consequences may ensue. In particular, EBV is associated with a variety of malignancies in which it appears to have an essential etiological role. However, it is now clear that the etiology of these diseases is extremely complex and that EBV is one among a series of essential factors required for the eventual outgrowth of the malignant cell. Several of these factors have now been clarified at the molecular level, although there remain many facets yet to be elucidated. The purpose of this chapter is to review EBV-associated tumors with emphasis on the oncogenic mechanisms involved.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Given, D., and Kieff, E., 1978, DNA of Epstein-Barr virus. IV Linkage map for restriction enzyme fragments of the B95-8 and Wai strains of EBV, J. Virol. 21:524–542.

    Google Scholar 

  2. Dambaugh, T., Beisel, C., Hummel, M., King, W., Fennewald, S., Cheung, A., Heller, M., Raab-Traub, N., and Kieff E., 1980, EBV DNA. VII Molecular cloning and detailed mapping of EBV (B95-8) DNA, Proc. Natl. Acad. Sci. USA 77:2999–3003.

    Article  PubMed  CAS  Google Scholar 

  3. Baer, R., Bankier, A. T., Biggin, M. D., Deininger, P. L., Farrell, P. J., Gibson, T. J., Hatfull, G., Hudson, G. S., Satchwell, S. C., Seguin, C., Tuffnell, P. S., and Barrell, B. G., 1984, DNA sequence and expression of the B95-8 Epstein-Barr virus genome, Nature 310:207–211.

    Article  PubMed  CAS  Google Scholar 

  4. Dambaugh, T., Wang, E., Hennessy, K., Woodland, E., Rickinson, A., and Kieff, E., 1986, Expression of the Epstein-Barr virus nuclear protein 2 in rodent cells, J. Virol. 59:453–462.

    PubMed  CAS  Google Scholar 

  5. Arrand, J. R., Young, L. S., and Tugwood, J. D., 1989, Two families of sequences in the small RNA-encoding region of Epstein-Barr virus (EBV) correlate with EBV types A and B, J. Virol. 63:983–986.

    PubMed  CAS  Google Scholar 

  6. Rowe, M., Young, L. S., Cadwallader, K., Petti, L., and Kieff, E., 1989, Distinction between Epstein-Barr virus type A (EBNA 2A) and type B (EBNA 2B) isolates extends to the EBNA 3 family of nuclear proteins, J. Virol 63:1031–1039.

    PubMed  CAS  Google Scholar 

  7. Rickinson, A. B., Young, L. S., and Rowe, M., 1987, Influence of the Epstein-Barr virus nuclear antigen EBNA2 on the growth phenotype of virus-transformed B cells, J. Virol 61:1310–1317.

    PubMed  CAS  Google Scholar 

  8. Zimber, U., Adldinger, H. K., Lenoir, G. M., Vuillauma, M., Knebel-Doeberitz, M. V., Laux, G., Desgranges, C., Wittmann, P., Freese, U.-K., Schneider, U., and Bornkamm, G. W., 1986, Geographical prevalence of two types of Epstein-Barr virus, Virology 154:56–66.

    Article  PubMed  CAS  Google Scholar 

  9. Sculley, T. B., Apolloni, A., Hurren, L., Moss, D. J., and Cooper, D. A., 1990, Coinfection with A-and B-type Epstein-Barr virus in human immunodeficiency virus-positive subjects, J. Infect. Dis. 162:643–648.

    Article  PubMed  CAS  Google Scholar 

  10. Frank, A., Ambiman, W., and Miller, G., 1976, Epstein-Barr virus and non-human primates: Natural and experimental infection, Adv. Cancer Res. 23:171–210.

    Article  PubMed  CAS  Google Scholar 

  11. Pattengale, P. K., Smith, R. W., and Gerber, P., 1973, Selective transformation of B lymphocytes by EB virus, Lancet 2:93–94.

    Article  PubMed  CAS  Google Scholar 

  12. Pope, J. H., Home, M. K., and Scott, W., 1968, Transformation of foetal human leucocytes in vitro by filtrates of a human leukaemia cell line containing herpes-like virus, Int. J. Cancer 3:857–866.

    Article  PubMed  CAS  Google Scholar 

  13. Sixbey, J. W., Vesterinen, E. H., Nedrud, J. G., Raab-Traub, N., Walton, L. A., and Pagano, J. S., 1983, Replication of Epstein-Barr virus in human epithelial cells infected in vitro, Nature 306:480–483.

    Article  PubMed  CAS  Google Scholar 

  14. Tosato, G., Blaese, M. R., and Yarchoan, R., 1985, Relationship between immunoglobulin production and immortalization by Epstein-Barr virus, J. Immunol. 135:959–964.

    PubMed  CAS  Google Scholar 

  15. Steel, C. M., Philipson, J., Arthur, E., Gardiner, S. E., Newton, M. S., and Mclntosh, R. V., 1977, Possibility of EB virus preferentially transforming a subpopulation of human B lymphocytes, Nature 270:729–731.

    Article  PubMed  CAS  Google Scholar 

  16. Nemerow, G. R., Wolfert, R., McNaughton, M. E., and Cooper, N. R., 1985, Identification and charactertisation of the Epstein-Barr virus receptor on human B lymphocytes and its relationship to the C3d complement receptor (CR2), J. Virol. 55:347–351.

    PubMed  CAS  Google Scholar 

  17. Bradbury, L. E., Kansas, G. S., Levy, S., Evans, R. L., and Tedder, T. T., 1992, The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of anti proliferative antibody-1 and Leu-13 molecules, J. Immunol 149:2841–2850.

    PubMed  CAS  Google Scholar 

  18. Hammerschmidt, W., and Sugden, B., 1989, Genetic analysis of immortalising functions of Epstein-Barr virus in human B lymphocytes, Nature 340:393–397.

    Article  PubMed  CAS  Google Scholar 

  19. Cohen, J. I., Wang, F., Mannick, J., and Kieff, E., 1989, Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation, Proc. Natl Acad. Sci. USA 86:9558–9562.

    Article  PubMed  CAS  Google Scholar 

  20. Tomkinson, B., Robertson, E., and Kieff, E., 1993, Epstein-Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation, J. Virol 67:2014–2025.

    PubMed  CAS  Google Scholar 

  21. Kaye, K. M., Izumi, K. M., and Kieff, E., 1993, Epstein-Barr virus latent membrane protein 1 is essential for B lymphocyte growth transformation, Proc. Natl Acad. Sci. USA 90:9150–9154.

    Article  PubMed  CAS  Google Scholar 

  22. Tomkinson, B., and Kieff, E., 1992, Use of second-site homologous recombination to demonstrate that Epstein-Barr virus nuclear protein 3B is not important for lymphocyte infection or growth transformation in vitro, J. Virol 66:2893–2903.

    PubMed  CAS  Google Scholar 

  23. Longnecker, R., Miller, C. L., Tomkinson, B., Miao, X-Q., and Kieff, E., 1993, Deletion of DNA encoding the first five transmembrane domains of Epstein-Barr virus latent membrane proteins 2A and 2B, J. Virol. 67:5068–5074.

    PubMed  CAS  Google Scholar 

  24. Kim, O.-J., and 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.

    PubMed  CAS  Google Scholar 

  25. Swaninathan, S., Tomkinson, B., and Kieff, E., 1991, Recombinant Epstein-Barr virus with small RNA (EBER) genes deleted transforms lymphocytes and replicates in vitro, Proc. Natl. Acad. Sci. USA 88:15446–1550.

    Google Scholar 

  26. Karran, L., Gao, Y., Smith, P. R., and Griffin, B. E., 1992, Expression of a family of complementary-strand transcripts in Epstein-Barr virus-infected cells, Proc. Natl. Acad. Sci. USA 89:8058–5062.

    Article  PubMed  CAS  Google Scholar 

  27. Smith, P., Gao, Y., Karran, L. Jones, M. D., Snudden, D., and Griffin, B. E., 1993, Complex nature of the major viral polyadenylated transcripts in Epstein-Barr virus-associated tumors, J. Virol. 67:3217–3225.

    PubMed  CAS  Google Scholar 

  28. Alfieri, C., Birkenbach, M., and Kieff, E., 1991, Early events in Epstein-Barr virus infection of human B lymphocytes, Virology 181:595–608.

    Article  PubMed  CAS  Google Scholar 

  29. Jiang, W.-Q., Szekely, L., Wendel-Hausen, V., Ringertz, N., Klein, G., and Rosen, A., 1991, Colocalisation of the retinobastoma protein and the Epstein-Barr virus-encoded nuclear antigen EBNA-5, Exp. Cell Res. 197:314–318.

    Article  PubMed  CAS  Google Scholar 

  30. Szekely, L., Seiivanova, G., Magnusson, K. P., Klein, G., and Wiman, K. G., 1993, EBNA-5, an Epstein-Barr virus-encoded nuclear antigen, binds to the retinoblastoma and p53 proteins, Proc. Natl. Acad. Sci. USA 90:5455–5459.

    Article  PubMed  CAS  Google Scholar 

  31. Woisetschlaeger, M. Jin, X. W., Yandava, C. N., Furmanski, L. A., Strominger, J. L., and Speck, S. H., 1991, Role for the Epstein-Barr virus nuclear antigen 2 in viral promoter switching during initial stages of infection, Proc. Natl. Acad. Sci. USA 88:3942–3946.

    Article  PubMed  CAS  Google Scholar 

  32. Fahraeus, R., Jansson, A., Ricksten, A., Sjoblom, A., and Rymo, L., 1990, Epstein-Barr virus-encoded nuclear antigen 2 actives the viral latent membrane protein promoter by modulating the activity of a negative regulatory element, Proc. Natl. Acad. Sci. USA 87:7390–7394.

    Article  PubMed  CAS  Google Scholar 

  33. Zimber-Strobl, U., Kremmer, E., Grässer, F., Marschall, G., Laux, G., and Bornkamm, G. W., 1993, The Epstein-Barr virus nuclear antigen 2 interacts with an EBNA2 responsive cis-element of the terminal protein 1 gene promoter, EMBO J. 12:167–175.

    PubMed  CAS  Google Scholar 

  34. Knutson, J. C., 1990, The level of c-fgr RNA is increased by EBNA2, an Epstein-Barr virus gene required for B cell immortalisation, J. Virol. 64:2530–2536.

    PubMed  CAS  Google Scholar 

  35. Finke, J., Fritzen, R., Ternes, P., Trivedi, P., Bross, K.J., Lange, W., Mertelsmann, R., and Dölken, G., 1992, Expression of bcl-2 in Burkitt’s lymphoma cell lines: Induction by latent Epstein-Barr virus genes, Blood 80:459–469.

    PubMed  CAS  Google Scholar 

  36. Wang, F., Gregory, C., Sample, C., Rowe, M., Liebowitz, D., Murray, R., Rickinson, A. G., and Kieff, E., 1990, Epstein-Barr virus latent membrane protein (LMP1) and nuclear protein 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23, J. Virol. 64:2309–2318.

    PubMed  CAS  Google Scholar 

  37. Thorley-Lawson, D. A., and Mann, K. P., 1985, Early events in Epstein-Barr virus infection provide a model for B cell activation. J. Exp. Med. 162:45–59.

    Article  PubMed  CAS  Google Scholar 

  38. Conrad, D. H., 1990, The low affinity receptor for IgE, Annu. Rev. Immunol. 8:623.

    Article  PubMed  CAS  Google Scholar 

  39. Swenderman, S., and Thorley-Lawson, D. A., 1987, The activation antigen BLAST-2, when shed, is an autocrine BCGF for normal and transformed B cells, EMBO J. 6:1637–1642.

    Google Scholar 

  40. Ling, P. D., Hsieh, J. J.-D., Ruf, I. K., Rawlins, D. R., and Hayward, S. D., 1994, EBNA-2 upregulation of Epstein-Barr virus latency promoters and the cellular CD23 promoter utilizes a common targeting intermediate, CBF1, J. Virol. 68:5375–5383.

    PubMed  CAS  Google Scholar 

  41. Waltzer, L., Logeat, F., Brou, C., Israel, A., Sergeant, A., and Manet, E., 1994, The human Jk recombination signal sequence binding protein (RBP-Jk) targets the Epstein-Barr virus EBNA 2 protein to its DNA responsive elements, EMBO J. 13:5633–5638.

    PubMed  CAS  Google Scholar 

  42. Johannesen, E., Koh, E., Mosialos, G., Tong, X., Keiff, E., and Grossman, S. R., 1995, Epstein-Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by Jk and PU1, J. Virol. 69:253–262.

    Google Scholar 

  43. Allday, M. J., Crawford, D. H., and Griffin, B. E., 1989, Epstein-Barr virus latent gene expression during the initiation of B cell immortalisation, J. Gen. Virol. 70:1755–1764.

    Article  PubMed  CAS  Google Scholar 

  44. Yates, J. L., Warren, N., and Sugden, B., 1985, Stable replication of plasmids derived from Epstein-Barr virus in mammalian cells, Nature 313:812–815.

    Article  PubMed  CAS  Google Scholar 

  45. Allday, M. J., Crawford, D. H., and Thomas, J. A., 1993, Epstein-Barr virus (EBV) nuclear antigen 6 induces expression of the EBV latent membrane protein and an activated phenotype in Raji cells, J. Gen. Virol. 74:361–369.

    Article  PubMed  CAS  Google Scholar 

  46. Wang, D., Liebowitz, D., and Kieff, E., 1985, An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells, Cell 43:831–840.

    Article  PubMed  CAS  Google Scholar 

  47. Wang, D., Liebowitz, D., Wang, F., Gregory, C., Rickinson, A., Larson, R., Springer, T., and Kieff, E., 1988, Epstein-Barr virus latent infection membrane protein alters the human B-lymphocyte phenotype: Deletion of the amino terminus abolishes activity, J. Virol. 62:4137–4184.

    Google Scholar 

  48. Henderson, S., Rowe, M., Gregory, C., Croom-Carter, D., Wang, F., Longnecker, R., Kieff, E., and 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.

    Article  PubMed  CAS  Google Scholar 

  49. Hammarskjold, M.-L., and Simurdo, M. C., 1992, Epstein-Barr virus latent membrane protein trans-activates the human immunodeficiency virus type I long terminal repeat through induction of NF-kB activity, J. Virol. 66:6496–6501.

    PubMed  CAS  Google Scholar 

  50. Moorthy, R., and Thorley-Lawson, D. A., 1990, Processing of the Epstein-Barr virus-encoded latent membrane protein P63/LMP, J. Virol. 64:829–837.

    PubMed  CAS  Google Scholar 

  51. Baichwal, V. R., and 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.

    PubMed  CAS  Google Scholar 

  52. Moorthy, R. K., and Thorley-Lawson, D. A., 1993, 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.

    PubMed  CAS  Google Scholar 

  53. Huen, D. S., Henderson, S. A., Croom-Carter, D., and Rowe, M., The Epstein-Barr virus latent membrane protein-1 (LMP1) mediates activation of NK-kB and cell surface phenotype via two effector regions in its carboxy-terminal cytoplasmic domain, Oncogene 10(3):549-560.

    Google Scholar 

  54. Laux, G., Perricaudet, M., and 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.

    PubMed  CAS  Google Scholar 

  55. Longnecker, R., Druker, B., Roberts, T., and Kieff, E., 1991, An Epstein-Barr virus protein associated with cell growth transformation interacts with a tyrosine kinase, J. Virol. 65:3681–3692.

    PubMed  CAS  Google Scholar 

  56. Miller, C. L., Lee, J. H., Kieff, E., and Longnecker, R., 1994, An integral membrane protein (LMP2) blocks reactivation of Epstein-Barr virus from latency following surface immunoglobulin crosslinking, Proc. Natl. Acad. Sci. USA 91:772–776.

    Article  PubMed  CAS  Google Scholar 

  57. Nilsson, K., Klein, G., Henle, W., and Henle, G., 1971, The establishment of lymphoblastoid lines from adult and foetal human lymphoid cells and its dependence on EBV, Int. J. Cancer 8:443–450.

    PubMed  CAS  Google Scholar 

  58. Crawford, D. H., and Ando, I., 1986, EB virus induction is associated with B cell maturation, Immunology 59:405–409.

    PubMed  CAS  Google Scholar 

  59. Zur Hausen, H., O’Neill, F. J., and Freese, U. K., 1978, Persisting oncogenic herpesvirus induced by the tumour promoter TPA, Nature 272:373–375.

    Article  PubMed  CAS  Google Scholar 

  60. Luka, J., Kallin, B., and Klein, G., 1979, Induction of the Epstein-Barr virus (EBV) cycle in latently infected cells by n-butyrate, Virology 94:228–231.

    Article  PubMed  CAS  Google Scholar 

  61. Tovey, M. G., Lenoir, G., and Begon-Lours, J., 1978, Activation of latent Epstein-Barr virus by antibody to human IgM, Nature 276:270–272.

    Article  PubMed  CAS  Google Scholar 

  62. Flemington, E., and Speck, S. H., 1990, Identification of phorbol ester response elements in the promotor of Epstein-Barr virus putative lytic switch gene BZLF1, J. Virol. 64:1217–1226.

    PubMed  CAS  Google Scholar 

  63. Grogan, E., Jenson, H., Countryman, J., Heston, L., Gradoville, L., and Miller, G., 1987, Transfection of a rearranged viral DNA fragment, WZhet, stably converts latent Epstein-Barr virus infection to productive infection in lymphoid cells, Proc. Natl. Acad. Sci. USA 84:1332–1336.

    Article  PubMed  CAS  Google Scholar 

  64. Niederman, J. C., Evans, A. S., Subrahmanyan, L., and McCollum, R. W., 1970, Prevalence, incidence and persistence of EB virus antibody in young adults, N. Engl. J. Med. 282:361–365.

    Article  PubMed  CAS  Google Scholar 

  65. Klein, G., Svedmyr, E., Jondal, U., and Persson, P. O., 1976, EBV-determined nuclear antigens (EBNA)-positive cells in the peripheral blood of infectious mononucleosis patients, Int. J. Cancer 17:21–26.

    Article  PubMed  CAS  Google Scholar 

  66. Tierney, R. J., Steven, N., Young, L. S., and Rickinson, A. B., 1994, Epstein-Barr virus latency in blood mononuclear cells: Analysis of viral gene transcription during primary infection and in the carrier state, J. Virol 68:7374–7385.

    PubMed  CAS  Google Scholar 

  67. Lam, K. M.-C., Whittle, H., Grzywacz, M., and Crawford, D. H., 1994, Epstein-Barr virus carrying B cells are large, surface IgM, IgD bearing cells in normal individuals and acute malaria patients, Immunology 82:383–388.

    PubMed  CAS  Google Scholar 

  68. Moss, D. J., Rickinson, A. B., and Pope, J. H., 1978, Long-term T-cell-mediated immunity to Epstein-Barr virus in man. I. Complete regression of virus-induced transformation in cultures of seropositive donor leucocytes, Int. J. Cancer 22:662–668.

    Article  PubMed  CAS  Google Scholar 

  69. Murray, R. J., Kurilla, M. G., Brooks, J. M., Thomas, W. A., Rowe, M., Kieff, E., and Rickinson, A. B., 1992, Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): Implication for the immune control of EBV-positive malignancies. J. Exp. Med. 176:157–168.

    Article  PubMed  CAS  Google Scholar 

  70. Klein, G., 1989, Viral latency and transformation: The strategy of Epstein-Barr virus, Cell 58:5–8.

    Article  PubMed  CAS  Google Scholar 

  71. Allday, M. J., and Crawford, D. H., 1988, The role of epithelium in EBV persistence and the pathogenesis of B cell tumours, Lancet 1:855–858.

    Article  PubMed  CAS  Google Scholar 

  72. Sixbey, J. W., 1989, Epstein-Barr virus and epithelial cells, Adv. Viral Oncol. 8:187–202.

    Google Scholar 

  73. Li, Q. X., Young, L. S., Niedobitek, G., Dawson, C. W., Birkenbach, M., Wang, F., and Richinson, A. B., 1992, Epstein-Barr virus infection and replication in a human epithelial cell system, Nature 356:347–350.

    Article  PubMed  CAS  Google Scholar 

  74. Qu, L., and Rowe, D. T., 1992, Epstein-Barr virus latent gene expression in uncultured peripheral blood lymphocytes, J. Virol. 66:3715–3724.

    PubMed  CAS  Google Scholar 

  75. Farrell, P. J., and Sinclair, A. J., 1994, Burkitt’s lymphoma, in: Viruses and Cancer, Vol. 51 (A. Mison, J. Neil, and M. McCrae, eds.), Cambridge University Press, Cambridge, pp. 101–121.

    Google Scholar 

  76. Thomas, J. A., Allday, M. J., and Crawford, D. H., 1991, Epstein-Barr virus-associated lympho-proliferative disorders in immunocompromised individuals, Adv. Cancer Res. 57:329–380.

    Article  PubMed  CAS  Google Scholar 

  77. Herbst, H., and Niedobitek, G., 1994, Epstein-Barr virus in Hodgkin’s disease, Epstein-Barr Virus Rep. 1:31–35.

    Google Scholar 

  78. Raab-Traub, N., 1992, The Epstein-Barr virus and nasopharyngeal carcinoma, in: Seminars in Cancer Biology, Vol. 3 (A. B. Rickinson, ed.), Saunders Scientific Publications/Academic Press, London, pp. 297–307.

    Google Scholar 

  79. Thomas, J. A., Cotter, F., Hanby, A. M., Long, L. Q., Morgan, P. R., Bramble, B., and Bailey, B. M. W., 1993, Epstein-Barr virus-related oral T-cell lymphoma associated with human immunodeficiency virus immunosuppression, Blood 81:3350–3356.

    PubMed  CAS  Google Scholar 

  80. Jones, J. F., Shurin, S., Abramowsky, C., Tubbs, R. R., Sciotto, C. G., Wahl, R., Sands, J., Gottman, D., Katz, B. Z., and Sklar, J., 1988, T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections, N. Engl. J. Med. 318:733–741.

    Article  PubMed  CAS  Google Scholar 

  81. Imai, S., Koizumi, S., Sujuira, M., Tokunaja, M., Uemura, Y., Yamamoto, N., Tanaka, S., Sato, E., and Osato, T., 1994, Gastric carcinoma: Monoclonal epithelium malignant cells expressing Epstein-Barr virus latent infection protein, Proc. Natl. Acad. Sci. USA 91:9131–9135.

    Article  PubMed  CAS  Google Scholar 

  82. Raab-Traub, N., Rajadurai, P., Flynn, K., and Lanier, A. P., 1991, Epstein-Barr virus infection in carcinoma of the salivary glands, J. Virol. 65(12):7032–7036.

    PubMed  CAS  Google Scholar 

  83. McClain, K. L., Leach, C. T., Jenson, H. B., Joshi, V. V., Pollock, B. H., Parniley, R. T., DiCarlo, E J., Gould Chadwick, E., and Murphy, S. B., 1995, Association of Epstein-Barr virus with leiomyosarcoma in young people with AIDS, N. Engl. J. Med. 332:12–18.

    Article  PubMed  CAS  Google Scholar 

  84. Lee, E. S., Locker, J., Nalesnik, M., Reyes, J., Jaffe, R., Alashari, M., Nour, B., Tzakis, A., and Dickman, P. S., 1995, The association of Epstein-Barr virus with smooth-muscle tumors occurring after organ transplantation, N. Engl. J. Med. 332:19–25.

    Article  PubMed  CAS  Google Scholar 

  85. Crawford, D. H., Sweny, P., Edwards, J. M. B., Janossy, G., and Hoffbrand, A. V., 1981, Longterm T-cell-mediated immunity to Epstein-Barr virus in renal-allograft recipients receiving cyclosporin A, Lancet 1:10–12.

    Article  PubMed  CAS  Google Scholar 

  86. Opelz, G., and Henderson, R., 1993, Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients, Lancet 342:1514–1516.

    Article  PubMed  CAS  Google Scholar 

  87. Thomas, J. A., Hotchin, N., Allday, M. J., Amlot, P., Rose, M., Yacoub, M., and Crawford, D. H., 1990, Immunohistology of Epstein-Barr virus associated antigens in B cell disorders from immunocompromised individuals, Transplantation 49:944–953.

    Article  PubMed  CAS  Google Scholar 

  88. Frizzera, G., 1987, The clinico-pathological expressions of Epstein-Barr virus infection in lymphoid tissues, Virchows Arch. [B] 53:1–12.

    Article  CAS  Google Scholar 

  89. Beral, V., Peterman, T., Berkelman, R., and Jaffe, H., 1991, AIDS-associated non-Hodgkin lymphoma, Lancet 337:805–809.

    Article  PubMed  CAS  Google Scholar 

  90. Ho, M., Jaffe, R., Miller, G., Breinig, M. K., Dummer, J. S., Makowka, L., Atchison, R. W., Karrer, F., Nalesnik, M. A., and Starzl, T. E., 1988, The frequency of Epstein-Barr virus infection and associated lymphoproliferative syndrome after transplantation and its manifestations in children, Transplantation 45:719–727.

    Article  PubMed  CAS  Google Scholar 

  91. Starzl, T E., Porter, K. A., Iwatsuki, S., Rosenthal, J. T., Shaw, B. W., Atchison, R. W., Nalesnik, M. A., Ho, M., Griffith, B. P., Hakala, T. R., Hardesty, R. L. Jaffe, R., and Bahnson, H. T., 1984, Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy, Lancet 1:583–587.

    Article  PubMed  CAS  Google Scholar 

  92. Armitage, J. M., Kormos, R. L., Stuart, S., Fricker, F.J., Griffith, B. P., Nalesnik, M., Hardesty, R. L., and Dummer, J. S., 1991, Posttransplant lymphoproliferative disease in thoracic organ transplant patients: Ten years of cyclosporine-based immunosuppression, J. Heart Lung Transplant 10:877–887.

    PubMed  CAS  Google Scholar 

  93. Rooney, C. M., Smith, C. A., Ng, C. Y. C., Loftin, S., Li, C., Krance, R. A., Brenner, M. K., and Heslop, H. E., 1995, Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr virus-related lymphoproliferation, Lancet 345:9–12.

    Article  PubMed  CAS  Google Scholar 

  94. Hartwell, L. H., and Castan, M. B., 1994, Cell cycle control and cancer, Science 266:1821–1828.

    Article  PubMed  CAS  Google Scholar 

  95. Epstein, M. A., and Barr, Y. M., 1964, Virus particles in cultured lymphoblasts from Burkitt’s lymphoma, Lancet 1:702–703.

    Article  PubMed  CAS  Google Scholar 

  96. Magrath, I., 1990, The pathogenesis of Burkitt’s lymphoma, Adv. Cancer Res. 55:130–270.

    Google Scholar 

  97. Burkitt, D., 1962, A children’s cancer dependent on climatic factors, Nature 194:232–234.

    Article  PubMed  CAS  Google Scholar 

  98. Epstein, M. A., and Achong, B. G., 1979, The relationship of the virus to Burkitt’s lymphoma, in: The Epstein-Barr Virus, (M. A. Epstein, and B. G. Achong, eds.), Springer, Berlin, pp. 321–337.

    Chapter  Google Scholar 

  99. Subar, M., Neri, A., Inghirami, G., Knowles, D. M., and Dalla-Favera, R., 1988, Frequent c-myc oncogenes activation and infrequent presence of Epstein-Barr virus genome in AIDS-associated lymphoma, Blood 72:667–671.

    PubMed  CAS  Google Scholar 

  100. Gregory, C. D., Edwards, C. F., Milner, A., Wiels, J., Lipinski, M., Rowe, M., Tursz, T., and Rickinson, A. B., 1988, Isolation of a normal B cell subset with a Burkitt-like phenotype and transformation in vitro with Epstein-Barr virus, Int. J. Cancer 42:213–220.

    Article  PubMed  CAS  Google Scholar 

  101. Raab-Traub, N., and Flynn, K., 1986, The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation, Cell 47:883–889.

    Article  PubMed  CAS  Google Scholar 

  102. Rowe, D. T., Rowe, M., Evans, G. I., Wallace, L. E., Farrell, P. J., and Rickinson, A. B., 1986, Restricted expression of EBV latent genes and T-lymphocyte-detected membrane antigen in Burkitt’s lymphoma cells, EMBO J. 5:2599–2607.

    PubMed  CAS  Google Scholar 

  103. Brooks, L. A., Lear, A. L., Young, L. S., and Rickinson, A. B., 1993, Transcripts from the Epstein-Barr virus BamHI A fragment are detectable in all three forms of virus latency, J. Virol. 67:3182–3190.

    PubMed  CAS  Google Scholar 

  104. Allday, M. J., Kundu, D., Finerty, S., and Griffin, B. E., 1990, CpG methylation of viral DNA in EBV-associated tumours, Int. J. Cancer 45:1125–1130.

    Article  PubMed  CAS  Google Scholar 

  105. Altiok, E., Minarovits, J., Hu, L. F., Contrerasbrodin, B., Klein, G., and Ernberg, I., 1992, Host-cell-phenotype-dependent control of the BCR2/BWR1 promoter complex regulates the expression of Epstein-Barr virus nuclear antigens 2-6, Proc. Natl Acad. Sci. USA 89:905–909.

    Article  PubMed  CAS  Google Scholar 

  106. Sample, J., Brooks, L., Sample, C., Young, L., Rowe, M., Gregory, C., Rickinson, A., and Kieff, E., 1991, Restricted Epstein-Barr virus protein expression in Burkitt lymphoma is due to a different Epstein-Barr virus nuclear antigen 1 transcriptional initiation site, Proc. Natl. Acad. Sci. USA 88:6343–6347.

    Article  PubMed  CAS  Google Scholar 

  107. Delecluse, H.-J., Bartnizke, S., Hammerschmidt, W., Bullerdiek, J., and Bornkamm, G. W., 1993, Episomal and integrated copies of Epstein-Barr virus coexist in Burkitt lymphoma cell lines, J. Virol. 67:1292–1299.

    PubMed  CAS  Google Scholar 

  108. Sixbey, J. W., 1994, Defective Epstein-Barr virus and viral disease processes, Epstein-Barr Virus Rep. 1:133–137.

    Google Scholar 

  109. Zimber-Strobl, U., Suentzenich, K.-O., Laux, G., Eick, D., Cordier, M., Calender, A., Billaud, M., Lenoir, G. M., and Bornkamm, G. W., 1991, Epstein-Barr virus nuclear antigen 2 activates transcription of the terminal protein gene, J. Virol. 65:415–423.

    PubMed  CAS  Google Scholar 

  110. Rowe, M., Lear, A. L., Croom-Carter, D., Davies, A. H., and Rickinson, A. B., 1992, Three pathways of Epstein-Barr virus gene activation from EBNAl-positive latency in B lymphocytes, J. Virol. 66:122–131.

    PubMed  CAS  Google Scholar 

  111. Rowe, M., Rowe, D. T., Gregory, C. D., Young, L. S., Farrell, P. J., Rupani, H., and Rickinson, A. B., 1987, Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt’s lymphoma cells, EMBO J. 6:2743–2751.

    PubMed  CAS  Google Scholar 

  112. Masucci, M. G., Contreras-Salazar, B., Ragnar, E., Falk, K., Minarovits, J., Ernberg, I., and Klein, G., 1989, 5-Azacytidine upregulates the expression of Epstein-Barr virus nuclear antigen 2 (EBNA2) through EBNA6 and latent membrane protein in the Burkitt’s lymphoma line Rael, J. Virol. 63:3135–3141.

    PubMed  CAS  Google Scholar 

  113. Shiramizu, B., Barriga, F., and Neequaye, J., 1991, Patterns of chromosomal breakpoint locations in Burkitt’s lymphoma: Relevance to geography and Epstein-Barr virus association, Blood 77:1516–1526.

    PubMed  CAS  Google Scholar 

  114. Neri, A., Barriga, F., Knowles, D. M., McGrath, I. T., and Dalla-Favera, R., 1988, Different regions of the immunoglobulin heavy-chain locus are involved in chromosomal translocations in distinct pathogenetic forms of Burkitt lymphoma, Proc. Natl. Acad. Sci. USA 85:2748–2752.

    Article  PubMed  CAS  Google Scholar 

  115. Kretzner, L., Blackwood, E. M., and Eisenman, R. N., 1992, Myc and max proteins possess distinct transcriptional activities, Nature 359:426–429.

    Article  PubMed  CAS  Google Scholar 

  116. Lombardi, L., Newcomb, E. W., and Dalla-Favera, R., 1989, Pathogenesis of Burkitt lymphoma: Expression of an activated c-myc oncogene causes the tumorigenic conversion of EBV-infected human B lymphoblasts, Cell 59:161–170.

    Google Scholar 

  117. Hotchin, N. A., Allday, M. J., and Crawford, D. H., 1990, Deregulated c-myc expression in Epstein-Barr virus-immortalised B-cells induces altered growth properties and surface phenotype but not tumorigenicity, Int. J. Cancer 45:566–571.

    Article  PubMed  CAS  Google Scholar 

  118. Langdon, W. Y., Harris, A. W., Cory, S., and Adams, J. M., 1986, The c-myc oncogene perturbs B lymphocyte development in Eμ-myc transgenic mice, Cell 47:11–18.

    Article  PubMed  CAS  Google Scholar 

  119. Rabbitts, T. H., Hamlyn, P. H., and Baer, R., 1983, Altered nucleotide sequences of a translocated c-myc gene in Burkitt lymphoma, Nature 306:760–765.

    Article  PubMed  CAS  Google Scholar 

  120. Vousden, K. H., Crook, T., and Farrell, P. J., 1993, Biological activities of p53 mutants in Burkitt’s lymphoma cells, J. Gen. Virol. 74:803–810.

    Article  PubMed  CAS  Google Scholar 

  121. Ho, M., Webster, H. K., Looareesuwan, S., Supanaranond, W., Phillips, R. E., Chanthavanich, P., and Warrell, D. A., 1986, Antigen-specific immunosuppression in human malaria due to P. falciparum, J. Infect. Dis. 153:763.

    Article  PubMed  CAS  Google Scholar 

  122. Greenwood, B. M., Oduloju, A. J., and Platts-Mills, T. A. E., 1979, Partial characterisation of a malaria mitogen, Trans. R. Soc. Trop. Med. Hyg. 73:178.

    Article  PubMed  CAS  Google Scholar 

  123. Clifford-Lane, H., Masur, H., Edgar, L. C., Whalen, G., Rook, A. H., and Fauci, A., 1983, Abnormalities of B cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome, N. Engl. J. Med. 309:453–458.

    Article  Google Scholar 

  124. Whittle, H. C., Brown, J., Marsh, K., Greenwood, B. M., Seidelin, P., Tighe, H., and Wedderburn, L., 1984, T-cell control of Epstein-Barr virus-infected B cells is lost during P. falciparum malaria, Nature 312:449–450.

    Article  PubMed  CAS  Google Scholar 

  125. Birx, D. L., Redfield, R. R., and Tosato, G., 1986, Defective regulation of Epstein-Barr virus infection in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related disorders, N. Engl. J. Med. 314:874–879.

    Article  PubMed  CAS  Google Scholar 

  126. Lam, K. M.-C., Syed, N., Whittle, H., and Crawford, D. H., 1991, Circulating Epstein-Barr virus-carrying B cells in acute malaria, Lancet 337:876–878.

    Article  PubMed  CAS  Google Scholar 

  127. Lenoir, G., and Bornkamm, G., 1987, Burkitt’s lymphoma, a human cancer model for the study of the multistep development of cancer: Proposal for a new scenario, Adv. Viral Oncol. 6:173–206.

    Google Scholar 

  128. MacMahon, B., 1957, Epidemiological evidence of the nature of Hodgkin’s disease, Cancer 10:1045–1054.

    Article  PubMed  CAS  Google Scholar 

  129. Rosdahl, N., Larsen, S. O., and Clemmesen, J., 1974, Hodgkin’s disease in patients with previous infectious mononucleosis: 30 years’ experience, Br. Med. J. 2:243–256.

    Article  Google Scholar 

  130. Mueller, N., 1991, An epidemiologist’s view of the new molecular biology findings in Hodgkin’s disease, Ann. Oncol. 2:23–28.

    Article  PubMed  Google Scholar 

  131. Weiss, L. M., Strikler, J. G., Warnke, R. A., Purtilo, D. T., and Sklar, J., 1987, Epstein-Barr viral DNA in tissues of Hodgkin’s disease, Am. J. Pathol. 129:86–91.

    PubMed  CAS  Google Scholar 

  132. Weiss, L. M., Movahed, L. A., Roger, B. S., Warnke, R. A., and Sklar, J., 1989, Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin’s disease. N. Engl. J. Med. 320:502–506.

    Article  PubMed  CAS  Google Scholar 

  133. Anagnostopoulos, I., Herbst, H., Niedobitek, G., and Stein, H., 1989, Demonstration of monoclonal EBV genomes in Hodgkin’s disease and KI-1-positive anaplasticiarge cell lymphoma in combined Southern blot and in situ hybridization. Blood 74:810–816.

    PubMed  CAS  Google Scholar 

  134. Pallesen, G., Hamilton-Dutoit, S. J., Rowe, M., and Young, L. S., 1991, Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin’s disease, Lancet 337:320–322.

    Article  PubMed  CAS  Google Scholar 

  135. Ambinder, R. F., Browing, P. J., Lorenzana, I., Leventhal, B. G., Cozenza, H., Mann, R. B., MacMahon, E. M. E., Medina, R., Cardona, V., Grufferman, S., Olshan, A., Levin, A., Petersen, E. A., Blattner, W., and Levine, P. H., 1993, Epstein-Barr virus and childhood Hodgkin’s disease in Honduras and the United States, Blood 81:462–467.

    PubMed  CAS  Google Scholar 

  136. Murray, P. G., Young, L. S., Rowe, M., and Crocker, J., 1992, Immunohistochemical demonstration of the Epstein-Barr virus-encoded latent membrane protein in paraffin sections of Hodgkin’s disease, J. Pathol. 166:1–5.

    Article  PubMed  CAS  Google Scholar 

  137. Chang, K. L., Albujar, P. E., Chen, Y. Y., Johnson, R. M., and Weiss, L. M., 1993, High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of Hodgkin’s disease occuring in Peru, Blood 81:496–501.

    PubMed  CAS  Google Scholar 

  138. Boyle, M. J., Vasak, E., Tschuchnigg, M., Turner, J. J., Sculley, T., Penny, R., Cooper, D. A., Tindall, B., and Sewell, W. A., 1993, Subtypes of Epstein-Barr virus (EBV) in Hodgkin’s disease: Association between B-type EBV and immunocompromise, Blood 81:468–474.

    PubMed  CAS  Google Scholar 

  139. Herbst, H., Steinbrecher, E., Niedobitek, G., Young, L. S., Brooks, L., Müller-Lantzsch, N., and Stein, H., 1992, Distribution and phenotype of Epstein-Barr virus-harboring cells in Hodgkin’s disease, Blood 80:484–491.

    PubMed  CAS  Google Scholar 

  140. O’Grady, J., Stewart, S., Elton, R. A., and Krajweski, A. S., 1994, EBV and Hogkin’s disease, Lancet 343:265–266.

    Article  PubMed  Google Scholar 

  141. Deacon, E. M., Pallesen, G., Niedobitek, G., Crocker, J., Brooks, L., Rickinson, A. B., and Young, L. S., 1993, Epstein-Barr virus and Hodgkin’s disease: Transcriptional analysis of virus latency in the malignant cells, J. Exp. Med. 177:339–349.

    Article  PubMed  CAS  Google Scholar 

  142. Pallesen, G., Sandvej, K., Hamilton-Dutoit, S. J., Rowe, M., and Young, L. S., 1991, Activation of Epstein-Barr virus replication in Hodgkin and Reed-Sternberg cells, Blood 78:1162–1165.

    PubMed  CAS  Google Scholar 

  143. Armstrong, A. A., Gallager, A., Krayewski, A. S., Jones, D. B., Wilkins, B. S., Onions, D. E., and Jarret, R. F., 1992, The expression of the EBV latent membrane protein (LMP-1) is independent of CD23 and bcl-2 in Reed-Sternberg cells in Hodgkin’s disease, Histopathology 21:72–73.

    Article  PubMed  CAS  Google Scholar 

  144. Knecht, H., Bachmann, E. Joske, D.J. L., Sahli, R., Emery-Goodman, A., Casanova, J.-L., Zilic, M., Bachmann, F., and Odermatt, B. F., 1993, Molecular analysis of the LMP (latent membrane protein) oncogene in Hodgkin’s disease, Leukemia 7:580–585.

    PubMed  CAS  Google Scholar 

  145. Henle, W., and Henle, G., 1976, Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma, Int. J. Cancer 17:1–7.

    Article  PubMed  CAS  Google Scholar 

  146. Wolf, H., Zur Hausen, H., and Becker, V., 1973, EB virus genomes in epithelial nasopharyngeal carcinoma cells, Nature [New Biol.] 244:245–247.

    CAS  Google Scholar 

  147. Huang, D. P., Ho, J. H. C., Henle, W., and Henle, G., 1974, Demonstration of Epstein-Barr virus associated nuclear antigen in nasopharyngeal carcinoma cells from fresh biopsies, Int. J. Cancer 14:580–588.

    Article  PubMed  CAS  Google Scholar 

  148. Klein, G., Giovanella, B. C., Landahl, T., Fialkow, P. J., Singh, S., and Stehlin, J., 1974, Direct evidence for the presence of Epstein-Barr virus DNA and nuclear antigen in malignant epithelial cells from patients with anaplastic carcinoma of the nasopharynx, Proc. Natl. Acad. Sci. USA 71:4737–4741.

    Article  PubMed  CAS  Google Scholar 

  149. Pathmanathan, K., Prasad, U., Flynn, K., Chandrika, M., and Raab-Traub, N., 1994, EBV infection in nasopharyngeal carcinoma and premalignant lesions: Gene expression and strain variation, in: Epstein-Barr Virus and Associated Diseases, (J. Pagano & A. Rickinson, eds.), Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, p. 238.

    Google Scholar 

  150. Lung, M. L., Chang, R. S., Huang, M. L., Guo, H.-Y., Choy, D., Sham, J., Tsao, S. Y., Cheng, P., and Ng, M. H., 1990, Epstein-Barr virus genotypes associated with nasopharyngeal carcinoma in Southern China, Virology 185:44–53.

    Article  Google Scholar 

  151. Lung, M. L., Lam, W.P., Sham J., Choy, D., Young-Sheng, Z., Guo, H.-Y., and Ng. M. H., 1991, Detection and prevelence of the “f” variant of Epstein-Barr virus in Southern China, Virobgy 185:67–71.

    CAS  Google Scholar 

  152. Hu, L.-F., Zabarovsky, E. R., Chen, F., Cao, S.-L., Ernberg, I., Klein, G., and 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.

    Article  PubMed  CAS  Google Scholar 

  153. Yao, K., Zhang, H.-Y., Zhu, H.-C., Wang, F.-X., Li, G.-Y., Wen, D.-S., Li, Y.-P., Tsai, C.-H.A., and Glaser, R., 1990, Establishment and characterization of two epithelial tumour cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus and derived from nasopharyngeal carcinoma, Int. J. Cancer 45:83–89.

    Article  PubMed  CAS  Google Scholar 

  154. Klein, G., Giovanella, B. C., Lindahl, T., Fialkow, P. J., Singh, S., and Stehlin, J., 1974, Direct evidence for the presence of Epstein-Barr virus DNA and nuclear antigen in malignant epithelial cells from patients with poorly differentiated carcinoma of the nasopharynx, Proc. Natl. Acad. Sci. USA 71:4737–4741.

    Article  PubMed  CAS  Google Scholar 

  155. Busson, P., Ganem, G., Flores, P., Mugneret, F., Clausse, B., Caillou, B., Braham, K., Wakasugi, H., Lipinski, M., and Tursz, T., 1988, Establishment and characterization of three transplantable EBV-containing nasopharyngeal carcinomas, Int. J. Cancer 42:599–606.

    Article  PubMed  CAS  Google Scholar 

  156. Brooks, L., Yao, Q. Y., Rickinson, A. B., and Young, L. S., 1992, Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts, J. Virol. 66:2689–2697.

    PubMed  CAS  Google Scholar 

  157. Cochet, C., Martel-Renoir, D., Grunewald, V., Bosq, J., Cochet, G., Schwaab, G. Bernaudin, J.-F., and Joab, I., 1993, Expression of the Epstein-Barr virus immediate early gene, BZLF1, in nasopharyngeal carcinoma tumor cells, Virology 197:358–365.

    Article  PubMed  CAS  Google Scholar 

  158. Fahraeus, R., Rymo, L., Rhim, J. S., and Klein, G., 1990, Morphological transformation of human keratinocytes expressing the LMP gene of Epstein-Barr virus, Nature 345:447–449.

    Article  PubMed  CAS  Google Scholar 

  159. Dawson, C. W., Rickinson, A. B., and Young, L. S., 1990, Epstein-Barr virus latent membrane protein inhibits human epithelial cell differentiation, Nature 344:777–780.

    Article  PubMed  CAS  Google Scholar 

  160. Wilson, J. B., Weinberg, W. Johnson, R., Yuspa, S., and 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.

    Article  PubMed  CAS  Google Scholar 

  161. Hu, L-F., Chen, F., Zheng, X., Ernberg, I., Cao, S.-L., Christensson, B., Klein, G., and Winberg, G., 1993, Clonability and tumorigenicity of human epithelial cells expressing the EBV encoded membrane protein LMP1, Oncogene 8:1575–1583.

    PubMed  CAS  Google Scholar 

  162. Nicholson, L., Hopwood, P., Johannessen, I., and Crawford, D. H., unpublished observation.

    Google Scholar 

  163. Lu, Q.-L., Elia, G., Lucas, S., and Thomas, J. A., 1993, Bcl-2 proto-oncogene expression in Epstein-Barr virus-associated nasopharyngeal carcinoma, Int. J. Cancer 53:29–35.

    Article  PubMed  CAS  Google Scholar 

  164. Effert, P., McCoy, R., Abdel-Hamid, M., Flynn, K., Zhang, Q., Busson, P., Tursz, T., Liu, E., and Raab-Traub, N., 1992, Alterations of the p53 gene in nasopharyngeal carcinoma, J. Virol. 66:3768–3775.

    PubMed  CAS  Google Scholar 

  165. Sun, Y., Hegamyer, G., Cheng, Y.-J., Hildesheim, A., Chen, J.-Y., Chen, I.-H., Cao, Y., Yao, K.-T., and Colburn, N. H., 1992, An infrequent point mutation of the p53 gene in human nasopharyngeal carcinoma, Proc. Natl. Acad. Sci. USA 89:6516–6520.

    Article  PubMed  CAS  Google Scholar 

  166. Niedobitek, G., Agathanggelou, A., Barber, P., Smallman, L., Jones, E., and Young, L., 1993, p53 overexpression and Epstein-Barr virus infection in undifferentiated and squamous cell nasopharyngeal carcinomas, J. Pathol. 170:457–461.

    Article  PubMed  CAS  Google Scholar 

  167. Thomas, J. A., Iliescu, V., Crawford, D. H., Ellouz, R., Cammoun, M., and De-Thé, G., 1984, Expression of HLA-DR antigens in nasopharyngeal carcinoma: An immunohistological analysis of the tumour cells and infiltrating lymphocytes, Int. J. Cancer 33:813–819.

    Article  PubMed  CAS  Google Scholar 

  168. Busson, P., Zhang, Q., Guillon, J.-M., Gregory, C. D., Young, L. S., Clausse, B., Lipinksi, M., Rickinson, A. B., and Tursz, T, 1992, Elevated expression ICAM1 (CD45) and minimal expression of LFA3 (CD58) in Epstein-Barr virus-positive nasopharyngeal carcinoma cells, Int. J. Cancer 50:863–867.

    Article  PubMed  CAS  Google Scholar 

  169. Simons, M. J., Wee, G. B., Chan, S. H., Shanmugaratnam, K., Day, N. E., and De-Thé, G. B., 1975, Probable identification of an HLA-A second-locus antigen associated with a high risk of nasopharyngeal carcinoma, Lancet 1:142–143.

    Article  PubMed  CAS  Google Scholar 

  170. Lu, S.-J., Day, N.E., Degos, L., Lepage, V., Wang, P.-C., Chan, S.-H., Simons, M., McKnight, B., Easton, D., Zeng, Y., and De Thé, G., 1990, Linkage of a nasopharyngeal carcinoma susceptibility locus to the HLA region, Nature 346:470–471.

    Article  PubMed  CAS  Google Scholar 

  171. Geser, A., Charney, N., Day, N. E., Ho, H. C., and De-Thé, G., 1978, Environmental features in the etiology of nasopharyngeal carcinoma, in: Nasopharyngeal Carcinoma: Etiology and Control (G. De-Thé and Y Ito, eds.) IARC Scientific Publications no. 20, Lyon, pp. 213–229.

    Google Scholar 

  172. Anderson, E. N. Jr., Anderson, M. L., and Ho, H. C., 1978, Environmental backgrounds of young Chinese nasopharyngeal carcinoma patients, in: Nasopharyngeal Carcinoma: Etiology and Control (G. De-Thé and Y Ito, eds.) IARC Scientific Publications no. 20, Lyon, pp. 231–239.

    Google Scholar 

  173. Huang, D. P., Ho, J. H. C., and Saw, D., and Teogh, T. B., 1978, Carcinoma of the nasal and paranasal regions in rats fed Cantonese salted marine fish, in: Nasopharyngeal Carcinoma: Etiology and Control (G. De-Thé and Y Ito, eds.) IARC Scientific Publications no. 20, Lyon, pp. 315–328.

    Google Scholar 

  174. Huang, D. P., Ho, J. H. C., Webb, K. S., Wood, B. J., and Gough, T. A., 1981, Volatile nitrosamines in salt-preserved fish before and after cooking, Fed. Cosmet. Toxicol. 19:167–171.

    Article  CAS  Google Scholar 

  175. Bouvier, G., Polack, A., Traub, B., Bornkamm, G. W., Ohshima, H., Bartsch, H., and De-Thé, G., 1988, Food extracts from high risk areas for NPC induce an EBV early promoter, in: Epstein-Barr Virus and Human Disease (D. V. Ablashi, A. Faggioni, G. R. F. Krueger, J. S. Pagano, and G. R. Pearson, eds.) Humana Press, Clifton, New Jersey, pp. 501–504.

    Google Scholar 

  176. Ito, Y, 1986, Vegetable activators of the viral genome and the causation of Burkitt’s lymphoma and nasopharyngeal carcinoma, in: The Epstein-Barr Virus (M. A. Epstein, and B. G. Achong, eds.), William Heineman, London, pp. 207–236.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, England

    Layla Karimi & Dorothy H. Crawford

Authors
  1. Layla Karimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dorothy H. Crawford
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Microbiology, School of Medicine, University of Ferrara, I-44100, Ferrara, Italy

    Giuseppe Barbanti-Brodano

  2. University of Pisa, Pisa, Italy

    Mauro Bendinelli

  3. University of South Florida, Tampa, Florida, USA

    Herman Friedman

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Karimi, L., Crawford, D.H. (1995). Epstein-Barr Virus. In: Barbanti-Brodano, G., Bendinelli, M., Friedman, H. (eds) DNA Tumor Viruses. Infectious Agents and Pathogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1100-1_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-1100-1_19

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-1102-5

  • Online ISBN: 978-1-4899-1100-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation