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. 1997 Nov;71(11):8928–8932. doi: 10.1128/jvi.71.11.8928-8932.1997

Bovine herpesvirus 4 BORFE2 protein inhibits Fas- and tumor necrosis factor receptor 1-induced apoptosis and contains death effector domains shared with other gamma-2 herpesviruses.

G H Wang 1, J Bertin 1, Y Wang 1, D A Martin 1, J Wang 1, K J Tomaselli 1, R C Armstrong 1, J I Cohen 1
PMCID: PMC192367  PMID: 9343261

Abstract

Fas- and tumor necrosis factor receptor 1 (TNFR1)-induced apoptosis is mediated by the interaction of FADD with caspase-8. Here, we report that the bovine herpesvirus 4 (BHV4) BORFE2 gene encodes a protein that inhibits Fas- and TNFR1-induced apoptosis and contains death effector domains (DEDs). Using the yeast two-hybrid system, we found that the BORFE2 protein interacts with the prodomain of caspase-8. Furthermore, we show that BHV4 BORFE2 is a member of a family of DED-containing proteins that includes other gamma-2 herpesviruses, such as Kaposi's sarcoma-associated herpesvirus and herpesvirus saimiri.

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Selected References

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  1. Afonso C. L., Neilan J. G., Kutish G. F., Rock D. L. An African swine fever virus Bc1-2 homolog, 5-HL, suppresses apoptotic cell death. J Virol. 1996 Jul;70(7):4858–4863. doi: 10.1128/jvi.70.7.4858-4863.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Albrecht J. C., Nicholas J., Biller D., Cameron K. R., Biesinger B., Newman C., Wittmann S., Craxton M. A., Coleman H., Fleckenstein B. Primary structure of the herpesvirus saimiri genome. J Virol. 1992 Aug;66(8):5047–5058. doi: 10.1128/jvi.66.8.5047-5058.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bertin J., Armstrong R. C., Ottilie S., Martin D. A., Wang Y., Banks S., Wang G. H., Senkevich T. G., Alnemri E. S., Moss B. Death effector domain-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosis. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1172–1176. doi: 10.1073/pnas.94.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bertin J., Mendrysa S. M., LaCount D. J., Gaur S., Krebs J. F., Armstrong R. C., Tomaselli K. J., Friesen P. D. Apoptotic suppression by baculovirus P35 involves cleavage by and inhibition of a virus-induced CED-3/ICE-like protease. J Virol. 1996 Sep;70(9):6251–6259. doi: 10.1128/jvi.70.9.6251-6259.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boldin M. P., Goncharov T. M., Goltsev Y. V., Wallach D. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell. 1996 Jun 14;85(6):803–815. doi: 10.1016/s0092-8674(00)81265-9. [DOI] [PubMed] [Google Scholar]
  6. Boldin M. P., Varfolomeev E. E., Pancer Z., Mett I. L., Camonis J. H., Wallach D. A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain. J Biol Chem. 1995 Apr 7;270(14):7795–7798. doi: 10.1074/jbc.270.14.7795. [DOI] [PubMed] [Google Scholar]
  7. Bump N. J., Hackett M., Hugunin M., Seshagiri S., Brady K., Chen P., Ferenz C., Franklin S., Ghayur T., Li P. Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35. Science. 1995 Sep 29;269(5232):1885–1888. doi: 10.1126/science.7569933. [DOI] [PubMed] [Google Scholar]
  8. Cheng E. H., Nicholas J., Bellows D. S., Hayward G. S., Guo H. G., Reitz M. S., Hardwick J. M. A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):690–694. doi: 10.1073/pnas.94.2.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chinnaiyan A. M., O'Rourke K., Tewari M., Dixit V. M. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell. 1995 May 19;81(4):505–512. doi: 10.1016/0092-8674(95)90071-3. [DOI] [PubMed] [Google Scholar]
  10. Debbas M., White E. Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B. Genes Dev. 1993 Apr;7(4):546–554. doi: 10.1101/gad.7.4.546. [DOI] [PubMed] [Google Scholar]
  11. Egyed L., Ballagi-Pordány A., Bartha A., Belák S. Studies of in vivo distribution of bovine herpesvirus type 4 in the natural host. J Clin Microbiol. 1996 May;34(5):1091–1095. doi: 10.1128/jcm.34.5.1091-1095.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Farrow S. N., White J. H., Martinou I., Raven T., Pun K. T., Grinham C. J., Martinou J. C., Brown R. Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K. Nature. 1995 Apr 20;374(6524):731–733. doi: 10.1038/374731a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Hsu H., Xiong J., Goeddel D. V. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell. 1995 May 19;81(4):495–504. doi: 10.1016/0092-8674(95)90070-5. [DOI] [PubMed] [Google Scholar]
  15. Hu S., Vincenz C., Buller M., Dixit V. M. A novel family of viral death effector domain-containing molecules that inhibit both CD-95- and tumor necrosis factor receptor-1-induced apoptosis. J Biol Chem. 1997 Apr 11;272(15):9621–9624. doi: 10.1074/jbc.272.15.9621. [DOI] [PubMed] [Google Scholar]
  16. Kawanishi M. Epstein-Barr virus BHRF1 protein protects intestine 407 epithelial cells from apoptosis induced by tumor necrosis factor alpha and anti-Fas antibody. J Virol. 1997 Apr;71(4):3319–3322. doi: 10.1128/jvi.71.4.3319-3322.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Lomonte P., Bublot M., van Santen V., Keil G. M., Pastoret P. P., Thiry E. Analysis of bovine herpesvirus 4 genomic regions located outside the conserved gammaherpesvirus gene blocks. J Gen Virol. 1995 Jul;76(Pt 7):1835–1841. doi: 10.1099/0022-1317-76-7-1835. [DOI] [PubMed] [Google Scholar]
  19. Muzio M., Chinnaiyan A. M., Kischkel F. C., O'Rourke K., Shevchenko A., Ni J., Scaffidi C., Bretz J. D., Zhang M., Gentz R. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex. Cell. 1996 Jun 14;85(6):817–827. doi: 10.1016/s0092-8674(00)81266-0. [DOI] [PubMed] [Google Scholar]
  20. Osorio F. A., Galeota-Wheeler J. A., Reed D. E., Lopez O. About the cellular tropism of the gammaherpesvirus bovine herpesvirus type 4. J Clin Microbiol. 1996 Dec;34(12):3253–3254. doi: 10.1128/jcm.34.12.3253-3254.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Osorio F. A., Rock D. L., Reed D. E. Studies on the pathogenesis of a bovine cytomegalo-like virus in an experimental host. J Gen Virol. 1985 Sep;66(Pt 9):1941–1951. doi: 10.1099/0022-1317-66-9-1941. [DOI] [PubMed] [Google Scholar]
  22. Pan H., Griep A. E. Altered cell cycle regulation in the lens of HPV-16 E6 or E7 transgenic mice: implications for tumor suppressor gene function in development. Genes Dev. 1994 Jun 1;8(11):1285–1299. doi: 10.1101/gad.8.11.1285. [DOI] [PubMed] [Google Scholar]
  23. Rao L., Debbas M., Sabbatini P., Hockenbery D., Korsmeyer S., White E. The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7742–7746. doi: 10.1073/pnas.89.16.7742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ray C. A., Black R. A., Kronheim S. R., Greenstreet T. A., Sleath P. R., Salvesen G. S., Pickup D. J. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell. 1992 May 15;69(4):597–604. doi: 10.1016/0092-8674(92)90223-y. [DOI] [PubMed] [Google Scholar]
  25. Russo J. J., Bohenzky R. A., Chien M. C., Chen J., Yan M., Maddalena D., Parry J. P., Peruzzi D., Edelman I. S., Chang Y. Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14862–14867. doi: 10.1073/pnas.93.25.14862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schreiber M., Sedger L., McFadden G. Distinct domains of M-T2, the myxoma virus tumor necrosis factor (TNF) receptor homolog, mediate extracellular TNF binding and intracellular apoptosis inhibition. J Virol. 1997 Mar;71(3):2171–2181. doi: 10.1128/jvi.71.3.2171-2181.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Srinivasula S. M., Ahmad M., Fernandes-Alnemri T., Litwack G., Alnemri E. S. Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14486–14491. doi: 10.1073/pnas.93.25.14486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Telford E. A., Watson M. S., Aird H. C., Perry J., Davison A. J. The DNA sequence of equine herpesvirus 2. J Mol Biol. 1995 Jun 9;249(3):520–528. doi: 10.1006/jmbi.1995.0314. [DOI] [PubMed] [Google Scholar]
  29. Teodoro J. G., Branton P. E. Regulation of apoptosis by viral gene products. J Virol. 1997 Mar;71(3):1739–1746. doi: 10.1128/jvi.71.3.1739-1746.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Thiry E., Bublot M., Dubuisson J., Van Bressem M. F., Lequarre A. S., Lomonte P., Vanderplasschen A., Pastoret P. P. Molecular biology of bovine herpesvirus type 4. Vet Microbiol. 1992 Nov;33(1-4):79–92. doi: 10.1016/0378-1135(92)90037-t. [DOI] [PubMed] [Google Scholar]
  31. Wang X. W., Gibson M. K., Vermeulen W., Yeh H., Forrester K., Stürzbecher H. W., Hoeijmakers J. H., Harris C. C. Abrogation of p53-induced apoptosis by the hepatitis B virus X gene. Cancer Res. 1995 Dec 15;55(24):6012–6016. [PubMed] [Google Scholar]
  32. Wong G. H., Goeddel D. V. Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons. 1986 Oct 30-Nov 5Nature. 323(6091):819–822. doi: 10.1038/323819a0. [DOI] [PubMed] [Google Scholar]

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