1887

Abstract

Tumour cells of undifferentiated nasopharyngeal carcinoma (NPC) consistently harbour Epstein–Barr virus (EBV) genes. Expression of mRNA transcripts associated with EBV latency has been demonstrated in such cells. However, expression of EBV lytic genes has not been well elucidated, although various lines of evidence have suggested that there is EBV replication in NPC tumour cells. We have studied mRNA expression of representative EBV lytic genes by RT–PCR in nasopharynx biopsies obtained from NPC and control individuals. In both NPC and control biopsies, EBV lytic genes BZLF1, BALF2 and BCLF1 were detected readily. However, BRLF1 was detected in NPC biopsies only. The BRLF1 gene was then cloned and expressed , and the protein product, Rta, was used as an antigen to detect specific antibodies by immunoprecipitation in plasma samples obtained from NPC patients and healthy controls. IgG antibodies directed against Rta were detected in 44 of 53 NPC plasma samples (83·0%), but only in 1 of 53 control samples (1·9%). Furthermore, the antibody binding regions were found in the C-terminal two-thirds of Rta. This serological result confirms indirectly that BRLF1 is specifically expressed in NPC tumour cells. Rta might play an important role in NPC pathogenesis, considering its multiple functions in EBV replication and cell cycles. Moreover, the detection of IgG antibodies directed against Rta could be developed into a diagnostic parameter for NPC.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-81-10-2417
2000-10-01
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/81/10/0812417a.html?itemId=/content/journal/jgv/10.1099/0022-1317-81-10-2417&mimeType=html&fmt=ahah

References

  1. Anagnostopoulos I., Hummel M., Kreschel C., Stein H. 1995; Morphology, immunophenotype and distribution of latently and/or productively Epstein–Barr virus-infected cells in acute infectious mononucleosis: implications for the inter-individual infection route of Epstein–Barr virus. Blood 85:744–750
    [Google Scholar]
  2. Babcock G. J., Decker L. L., Volk M., Thorley-Lawson D. A. 1998; EBV persistence in memory B cells in vivo . Immunity 9:395–404
    [Google Scholar]
  3. Brooks L., Yao Q. Y., Rickinson A. B., Young L. S. 1992; Epstein–Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. Journal of Virology 66:2689–2697
    [Google Scholar]
  4. Cox M. A., Leahy J., Hardwick J. M. 1990; An enhancer within the divergent promoter of Epstein–Barr virus responds synergistically to the R transactivators and Z transactivators. Journal of Virology 64:313–321
    [Google Scholar]
  5. Feng P., Chan S. H., Ooi E. E., Soo M. Y. R., Loh K. S., Wang D., Ren E. C., Hu H. Z. 1999; Elevated blood levels of soluble tumor necrosis factor receptors in nasopharyngeal carcinoma: correlation with humoral immune response to lytic replication of Epstein–Barr virus. International Journal of Oncology 15:167–172
    [Google Scholar]
  6. Gutsch D. E., Marcu K. B., Kenney S. C. 1994; The Epstein–Barr virus BRLF1 gene product transactivates the murine and human c- myc promoters. Cellular and Molecular Biology 40:747–760
    [Google Scholar]
  7. Henderson S., Huen D., Rowe M., Dawson C., Johnson G., Rickinson A. B. 1993; Epstein–Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proceedings of the National Academy of Sciences, USA 90:8479–8483
    [Google Scholar]
  8. Henle G., Henle W. 1976; Epstein–Barr virus specific IgA serum antibody as an outstanding feature of nasopharyngeal carcinoma. International Journal of Cancer 17:1–7
    [Google Scholar]
  9. Holley-Guthrie E. A., Quinlivan E. B., Mar E. C., Kenney S. C. 1990; The Epstein–Barr virus (EBV) BMRF1 promoter for early antigen (EA-D) is regulated by the EBV transactivators, BRLF1 and BZLF1, in a cell-specific manner. Journal of Virology 64:3753–3759
    [Google Scholar]
  10. Hu H. Z., Li G. L., Lim Y. K., Chan S. H., Yap E. H. 1999; Kinetics of interferon-γ secretion and its regulatory factors in the early phase of acute graft-versus-host disease. Immunology 98:379–385
    [Google Scholar]
  11. Kenney S., Holley-Guthrie E., Mar E. C., Smith M. 1989; The Epstein–Barr virus BMLF1 promoter contains an enhancer element that is responsive to the BZLF1 and BRLF1 transactivator. Journal of Virology 63:3878–3883
    [Google Scholar]
  12. Kieff E. 1996; Epstein–Barr virus and its replication. In Field’s Virology pp 2342–2396 Edited by Fields B. N., Knipe D. M., Howley P. M. Philadelphia: Lippincott–Raven;
    [Google Scholar]
  13. Liu D. X., Brierley I., Tibbles K. W., Brown T. D. K. 1994; A 100-kilodalton polypeptide encoded by open reading frame (OFR) 1b of the coronavirus infectious bronchitis virus is processed by ORF 1a products. Journal of Virology 68:5772–5780
    [Google Scholar]
  14. Liu C., Sista N. D., Pagano J. S. 1996; Activation of the Epstein–Barr virus DNA polymerase promoter by the BRLF1 immediate-early protein is mediated through USF and E2F. Journal of Virology 70:2545–2555
    [Google Scholar]
  15. Lo Y. M. D., Chan L. Y. S., Lo K. W., Leung S. F., Zhang J., Chan A. T. C., Lee J. C. K., Hjelm N. M., Johnson P. J., Huang D. P. 1999; Quantitative analysis of cell-free Epstein–Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Research 59:1188–1191
    [Google Scholar]
  16. Martelrenoir D., Grunewald V., Touitou R., Schwaab G., Joab I. 1995; Qualitative-analysis of the expression of Epstein-Barr-Virus lytic genes in nasopharyngeal carcinoma biopsies. Journal of General Virology 76:1401–1408
    [Google Scholar]
  17. Pepperl S., Benninger-Doring G., Modrow S., Wolf H., Jilg W. 1998; Immediate-early transactivator Rta of Epstein–Barr virus (EBV) shows multiple epitopes recognized by EBV-specific cytotoxic T lymphocytes. Journal of Virology 72:8644–8649
    [Google Scholar]
  18. Prang N. S., Hornef M. W., Jager M., Wagner H. J., Wolf H., Schwarzmann F. M. 1997; Lytic replication of Epstein–Barr virus in the peripheral blood: analysis of viral gene expression in B lymphocytes during infectious mononucleosis and in the normal carrier state. Blood 89:1665–1677
    [Google Scholar]
  19. Raab-Traub N., Flynn K. 1986; The structure of the termini of the Epstein–Barr virus as a marker of clonal cellular proliferation. Cell 47:883–889
    [Google Scholar]
  20. Ragoczy T., Heston L., Miller G. 1998; The Epstein–Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes. Journal of Virology 72:7978–7984
    [Google Scholar]
  21. Rickinson A., Kieff E. 1996; Epstein–Barr virus. In Field’s Virology pp 2397–2415 Edited by Fields B. N., Knipe D. M., Howley P. M. Philadelphia: Lippincott–Raven;
    [Google Scholar]
  22. Rodriguez A., Armstrong M., Dwyer D., Flemington E. 1999; Genetic dissection of cell growth arrest functions mediated by the Epstein–Barr virus lytic gene product, Zta. Journal of Virology 73:9029–9038
    [Google Scholar]
  23. Sixbey J. W., Nedrud J. G., Raab-Traub N., Hanes R. A., Pagano J. S. 1984; Epstein–Barr virus replication in oropharyngeal epithelial cells. New England Journal of Medicine 310:1225–1230
    [Google Scholar]
  24. Swenson J. J., Mauser A. E., Kaufmann W. K., Kenney S. C. 1999; The Epstein–Barr virus protein BRLF1 activates S phase entry through E2F1 induction. Journal of Virology 73:6540–6550
    [Google Scholar]
  25. Takada K., Ono Y. 1989; Synchronous and sequential activation of latently infected Epstein–Barr virus genomes. Journal of Virology 63:445–449
    [Google Scholar]
  26. Tang K. F., Chan S. H., Loh K. S., Chong S. M., Wang D. Y., Yeoh K. H., Hu H. Z. 1999; Increased production of interferon-γ by tumour infiltrating T lymphocytes in nasopharyngeal carcinoma: indicative of an activated status. Cancer Letters 140:93–98
    [Google Scholar]
  27. Thorley-Lawson D. A., Miyashita E. M., Khan G. 1996; Epstein–Barr virus and the B cell: that’s all it takes. Trends in Microbiology 4:204–208
    [Google Scholar]
  28. Tierney R. J., Steven N., Young L. S., 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. Journal of Virology 68:7374–7385
    [Google Scholar]
  29. Trumper P. A., Epstein M. A., Giovanella B. C., Finerty S. 1977; Isolation of infectious EB virus from the epithelial tumour cells of nasopharyngeal carcinoma. International Journal of Cancer 20:655–662
    [Google Scholar]
  30. Wolf H., zur Hausen H., Becker V. 1973; EB viral genomes in epithelial nasopharyngeal carcinoma cells. Nature 244:245–247
    [Google Scholar]
  31. Zacny V. L., Wilson J., Pagano J. S. 1998; The Epstein–Barr virus immediate-early gene product, BRLF1, interacts with the retinoblastoma protein during the viral lytic cycle. Journal of Virology 72:8043–8051
    [Google Scholar]
  32. Zalani S., Holley-Guthrie E., Kenney S. 1996; Epstein–Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism. Proceedings of the National Academy of Sciences, USA 93:9194–9199
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-81-10-2417
Loading
/content/journal/jgv/10.1099/0022-1317-81-10-2417
Loading

Data & Media loading...

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