1887

Abstract

Poxviruses encode multiple proteins that enable them to evade host responses. Among these are serine protease inhibitors (serpins). One of the earliest serpins described, cowpox virus crmA, acts to inhibit inflammation and apoptosis. crmA homologous serpins, known as SPI-2, are conserved in rabbitpox, vaccinia and variola viruses. Here, we describe the characterization of ectromelia virus (EV) SPI-2. EV SPI-2 encodes a protein of approximately 38 kDa showing >94% identity with other poxviral homologues. Conservative changes in amino acid sequence were found within the reactive site loop and the serpin backbone. Like crmA, transient expression of SPI-2 protected cells from tumour necrosis factor-mediated apoptosis and inhibited the activity of caspases-1 and -8 but not caspases-3, -6 or granzyme B. Overall, this study demonstrates that EV SPI-2 is functionally similar to crmA, based on assays.

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2000-10-01
2024-05-05
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References

  1. Blanden R. V. 1970; Mechanisms of recovery from a generalized viral infection: mousepox. Journal of Experimental Medicine 132:1035–1054
    [Google Scholar]
  2. Boldin M. P., Goncharov T. M., Goltsev Y. V., Wallach D. 1996; Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 85:803–815
    [Google Scholar]
  3. Buller R. M., Palumbo G. J. 1991; Poxvirus pathogenesis. Microbiological Reviews 55:80–122
    [Google Scholar]
  4. Cerretti D. P., Kozlosky C. J., Mosley B., Nelson N., Van Ness K., Greenstreet T. A., March C. J., Kronheim S. R., Druck T., Cannizzaro L. A. and others 1992; Molecular cloning of the interleukin-1 beta converting enzyme. Science 256:97–100
    [Google Scholar]
  5. Chen W., Drillien R., Spehner D., Buller R. 1992; Restricted replication of ectromelia virus in cell culture correlates with mutations in virus-encoded host range gene. Virology 187:433–442
    [Google Scholar]
  6. Chen N., Buller R. M., Wall E. M., Upton C. 2000; Analysis of host response modifier ORFs of ectromelia virus, the causative agent of mousepox. Virus Research 66:155–173
    [Google Scholar]
  7. Chinnaiyan A. M., O’Rourke K., Tewari M., Dixit V. M. 1995; FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81:505–512
    [Google Scholar]
  8. Chinnaiyan A. M., Tepper C. G., Seldin M. F., O’Rourke K., Kischkel F. C., Hellbardt S., Krammer P. H., Peter M. E., Dixit V. M. 1996; FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. Journal of Biological Chemistry 271:4961–4965
    [Google Scholar]
  9. Colussi P., Harvey N., Shearwin-Whyatt L., Kumar S. 1998; Conversion of procapsase-3 to an autoactivating caspase by fusion to the caspase-2 domain. Journal of Biological Chemistry 273:26566–26570
    [Google Scholar]
  10. Ekert P., Silke J., Vaux D. 1999; Inhibition of apoptosis and clonogenic survival of cells expressing crmA variants: optimal caspase substrates are not necessarily optimal inhibitors. EMBO Journal 18:330–338
    [Google Scholar]
  11. Garcia-Calvo M., Peterson E., Leiting B., Ruel R., Nicholson D., Thornberry N. 1998; Inhibition of human caspases by peptide-based and macromolecular inhibitors. Journal of Biological Chemistry 273:32608–32613
    [Google Scholar]
  12. Hsu H., Xiong J., Goeddel D. V. 1995; The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81:495–504
    [Google Scholar]
  13. Hsu H., Shu H. B., Pan M. G., Goeddel D. V. 1996; TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84:299–308
    [Google Scholar]
  14. Huang D., Cory S., Strasser A. 1997; Bcl-2, Bcl-x1 and adenovirus protein E1B19KD are functionally equivalent in their ability to inhibit cell death. Oncogene 14:405–414
    [Google Scholar]
  15. Karupiah G., Fredrickson T. N., Holmes K. L., Khairallah L. H., Buller R. M. 1993a; Importance of interferons in recovery from mousepox. Journal of Virology 67:4214–4226
    [Google Scholar]
  16. Karupiah G., Xie Q. W., Buller R. M., Nathan C., Duarte C., MacMicking J. D. 1993b; Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. Science 261:1445–1448
    [Google Scholar]
  17. Karupiah G., Buller R. M., Van Rooijen N., Duarte C. J., Chen J. 1996; Different roles for CD4+ and CD8+ T lymphocytes and macrophage subsets in the control of a generalized virus infection. Journal of Virology 70:8301–8309
    [Google Scholar]
  18. Kettle S., Blake N. W., Law K. M., Smith G. L. 1995; Vaccinia virus serpins B13R (SPI-2) and B22R (SPI-1) encode M(r) 38·5 and 40K, intracellular polypeptides that do not affect virus virulence in a murine intranasal model. Virology 206:136–147
    [Google Scholar]
  19. Kumar S., Kinoshita M., Noda M., Copeland N., Jenkins N. 1994; Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans death gene ced-3 and the mammalian IL-1β-converting enzyme. Genes & Development 8:1613–1626
    [Google Scholar]
  20. Martin S. J., Amarante-Mendes G. P., Shi L., Chuang T. H., Casiano C. A., O’Brien G. A., Fitzgerald P., Tan E. M., Bokoch G. M., Greenberg A. H., Green D. R. 1996; The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism. EMBO Journal 15:2407–2416
    [Google Scholar]
  21. Miura M., Friedlander R. M., Yuan J. 1995; Tumor necrosis factor-induced apoptosis is mediated by a CrmA-sensitive cell death pathway. Proceedings of the National Academy of Sciences, USA 92:8318–8322
    [Google Scholar]
  22. Mullbacher A., Hla R. T., Museteanu C., Simon M. M. 1999a; Perforin is essential for control of ectromelia virus but not related poxviruses in mice. Journal of Virology 73:1665–1667
    [Google Scholar]
  23. Mullbacher A., Wallich A., Moyer R., Simon M. 1999b; Poxvirus-encoded serpins do not prevent cytolytic T cell-mediated recovery from primary infections. Journal of Immunology 162:7315–7321
    [Google Scholar]
  24. Muzio M., Chinnaiyan A. M., Kischkel F. C., O’Rourke K., Shevchenko A., Ni J., Scaffidi C., Bretz J. D., Zhang M., Gentz R., Mann M., Krammer P. H., Peter M. E., Dixit V. M. 1996; FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell 85:817–827
    [Google Scholar]
  25. Newton K., Harris A. W., Bath M. L., Smith K. G. C., Strasser A. 1998; A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. EMBO Journal 17:706–718
    [Google Scholar]
  26. Palumbo G. J., Pickup D. J., Fredrickson T. N., McIntyre L. J., Buller R. M. 1989; Inhibition of an inflammatory response is mediated by a 38-kDa protein of cowpox virus. Virology 172:262–273
    [Google Scholar]
  27. Pickup D. J., Ink B. S., Hu W., Ray C. A., Joklik W. K. 1986; Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases. Proceedings of the National Academy of Sciences, USA 83:7698–7702
    [Google Scholar]
  28. Quan L. T., Caputo A., Bleackley R. C., Pickup D. J., Salvesen G. S. 1995; Granzyme B is inhibited by the cowpox virus serpin cytokine response modifier A. Journal of Biological Chemistry 270:10377–10379
    [Google Scholar]
  29. Ramshaw I. A., Ramsay A. J., Karupiah G., Rolph M. S., Mahalingam S., Ruby J. C. 1997; Cytokines and immunity to viral infections. Immunological Reviews 159:119–135
    [Google Scholar]
  30. Ray C. A., Black R. A., Kronheim S. R., Greenstreet T. A., Sleath P. R., Salvesen G. S., Pickup D. J. 1992; Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell 69:597–604
    [Google Scholar]
  31. Smyth M. J., Trapani J. A. 1995; Granzymes: exogenous proteinases that induce target cell apoptosis. Immunology Today 16:202–206
    [Google Scholar]
  32. Srinivasula S., Ahmad M., MacFarlane M., Luo Z., Huang Z., Fernandes-Alnemri T., Alnemri E. 1998; Generation of constitutively active recombinant caspases-3 and -6 by rearrangement of their subunits. Journal of Biological Chemistry 273:10107–10111
    [Google Scholar]
  33. Tartaglia L. A., Ayres T. M., Wong G. H., Goeddel D. V. 1993; A novel domain within the 55 kd TNF receptor signals cell death. Cell 74:845–853
    [Google Scholar]
  34. Tewari M., Dixit V. M. 1995; Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product. Journal of Biological Chemistry 270:3255–3260
    [Google Scholar]
  35. Tewari M., Telford W., Miller R., Dixit V. 1995; CrmA, a poxvirus-encoded serpin, inhibits cytotoxic T-lymphocyte-mediated apoptosis. Journal of Biological Chemistry 270:22705–22708
    [Google Scholar]
  36. Thornberry N. A., Bull H. G., Calaycay J. R., Chapman K. T., Howard A. D., Kostura M. J., Miller D. K., Molineaux S. M., Weidner J. R., Aunins J. and others 1992; A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356:768–774
    [Google Scholar]
  37. Turner P., Moyer R. 1998; Control of apoptosis by poxviruses. Seminars in Virology 8:453–469
    [Google Scholar]
  38. Wang S., Hawkins C., Yoo S., Muller H., Hay B. 1999; The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID. Cell 98:453–463
    [Google Scholar]
  39. Zhou Q., Snipas S., Orth K., Muzio M., Dixit V., Salvensen G. 1997; Target protease specificity of the viral serpin CrmA. Analysis of five caspases. Journal of Biological Chemistry 272:7797–7800
    [Google Scholar]
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