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. 1997 Apr;71(4):3319–3322. doi: 10.1128/jvi.71.4.3319-3322.1997

Epstein-Barr virus BHRF1 protein protects intestine 407 epithelial cells from apoptosis induced by tumor necrosis factor alpha and anti-Fas antibody.

M Kawanishi 1
PMCID: PMC191471  PMID: 9060702

Abstract

Tumor necrosis factor (TNF) and cytotoxic T lymphocytes, which utilize Fas to induce apoptosis in target cells, are known to play a critical role in the host defense against viral infection. In this study, the Epstein-Barr virus BHRF1 protein was stably expressed in intestine 407 cells which were susceptible to cell death mediated through both the TNF receptor and Fas. WST-1 conversion assays and acridine orange staining showed that vector-transfected control cells were killed by TNF-alpha or anti-Fas antibody in a dose-dependent manner, whereas BHRF1-expressing cells were resistant to apoptosis induced by these mediators. DNA fragmentation, a characteristic of apoptosis induced by TNF-alpha and the anti-Fas antibody, was suppressed in BHRF1-expressing cells. These results indicate that the BHRF1 protein protects cells from apoptosis mediated by the TNF receptor and Fas. The role of BHRF1 as an inhibitor of cytokine-induced apoptosis during the Epstein-Barr virus lytic cycle in vivo is discussed.

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Selected References

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  1. 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., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
  2. Cleary M. L., Smith S. D., Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986 Oct 10;47(1):19–28. doi: 10.1016/0092-8674(86)90362-4. [DOI] [PubMed] [Google Scholar]
  3. Dawson C. W., Eliopoulos A. G., Dawson J., Young L. S. BHRF1, a viral homologue of the Bcl-2 oncogene, disturbs epithelial cell differentiation. Oncogene. 1995 Jan 5;10(1):69–77. [PubMed] [Google Scholar]
  4. Field J., Nikawa J., Broek D., MacDonald B., Rodgers L., Wilson I. A., Lerner R. A., Wigler M. Purification of a RAS-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method. Mol Cell Biol. 1988 May;8(5):2159–2165. doi: 10.1128/mcb.8.5.2159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hanabuchi S., Koyanagi M., Kawasaki A., Shinohara N., Matsuzawa A., Nishimura Y., Kobayashi Y., Yonehara S., Yagita H., Okumura K. Fas and its ligand in a general mechanism of T-cell-mediated cytotoxicity. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4930–4934. doi: 10.1073/pnas.91.11.4930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Henderson S., Huen D., Rowe M., Dawson C., Johnson G., Rickinson A. Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8479–8483. doi: 10.1073/pnas.90.18.8479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
  8. Ju S. T., Cui H., Panka D. J., Ettinger R., Marshak-Rothstein A. Participation of target Fas protein in apoptosis pathway induced by CD4+ Th1 and CD8+ cytotoxic T cells. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4185–4189. doi: 10.1073/pnas.91.10.4185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kawanishi M. Epstein-Barr virus induces fragmentation of chromosomal DNA during lytic infection. J Virol. 1993 Dec;67(12):7654–7658. doi: 10.1128/jvi.67.12.7654-7658.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kägi D., Vignaux F., Ledermann B., Bürki K., Depraetere V., Nagata S., Hengartner H., Golstein P. Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science. 1994 Jul 22;265(5171):528–530. doi: 10.1126/science.7518614. [DOI] [PubMed] [Google Scholar]
  11. Lee M. A., Yates J. L. BHRF1 of Epstein-Barr virus, which is homologous to human proto-oncogene bcl2, is not essential for transformation of B cells or for virus replication in vitro. J Virol. 1992 Apr;66(4):1899–1906. doi: 10.1128/jvi.66.4.1899-1906.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Marchini A., Tomkinson B., Cohen J. I., Kieff E. BHRF1, the Epstein-Barr virus gene with homology to Bc12, is dispensable for B-lymphocyte transformation and virus replication. J Virol. 1991 Nov;65(11):5991–6000. doi: 10.1128/jvi.65.11.5991-6000.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nagata S., Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. doi: 10.1126/science.7533326. [DOI] [PubMed] [Google Scholar]
  14. Pearson G. R., Luka J., Petti L., Sample J., Birkenbach M., Braun D., Kieff E. Identification of an Epstein-Barr virus early gene encoding a second component of the restricted early antigen complex. Virology. 1987 Sep;160(1):151–161. doi: 10.1016/0042-6822(87)90055-9. [DOI] [PubMed] [Google Scholar]
  15. Pfitzner A. J., Tsai E. C., Strominger J. L., Speck S. H. Isolation and characterization of cDNA clones corresponding to transcripts from the BamHI H and F regions of the Epstein-Barr virus genome. J Virol. 1987 Sep;61(9):2902–2909. doi: 10.1128/jvi.61.9.2902-2909.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Stalder T., Hahn S., Erb P. Fas antigen is the major target molecule for CD4+ T cell-mediated cytotoxicity. J Immunol. 1994 Feb 1;152(3):1127–1133. [PubMed] [Google Scholar]
  17. Tarodi B., Subramanian T., Chinnadurai G. Epstein-Barr virus BHRF1 protein protects against cell death induced by DNA-damaging agents and heterologous viral infection. Virology. 1994 Jun;201(2):404–407. doi: 10.1006/viro.1994.1309. [DOI] [PubMed] [Google Scholar]
  18. Tartaglia L. A., Rothe M., Hu Y. F., Goeddel D. V. Tumor necrosis factor's cytotoxic activity is signaled by the p55 TNF receptor. Cell. 1993 Apr 23;73(2):213–216. doi: 10.1016/0092-8674(93)90222-c. [DOI] [PubMed] [Google Scholar]
  19. Trauth B. C., Klas C., Peters A. M., Matzku S., Möller P., Falk W., Debatin K. M., Krammer P. H. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science. 1989 Jul 21;245(4915):301–305. doi: 10.1126/science.2787530. [DOI] [PubMed] [Google Scholar]
  20. Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol. 1992;10:411–452. doi: 10.1146/annurev.iy.10.040192.002211. [DOI] [PubMed] [Google Scholar]
  21. Yonehara S., Ishii A., Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med. 1989 May 1;169(5):1747–1756. doi: 10.1084/jem.169.5.1747. [DOI] [PMC free article] [PubMed] [Google Scholar]

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