1887

Abstract

Hantaviruses are known to cause two severe human diseases: haemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. The mechanisms of pathogenesis of these two diseases are progressively becoming understood. Recently, two hantaviruses, Hantaan and Prospect Hill were reported to cause programmed cell death of Vero E6 cells. This study shows that Tula hantavirus (TULV) infection efficiently triggers an apoptotic programme in infected Vero E6 cells, and that the replication of TULV is required for the activation of caspase 3 and the cleavage of poly (ADP-ribose) polymerase, two molecular hallmarks of apoptosis. The enforced treatment of infected Vero E6 cells with tumour necrosis factor alpha (TNF-), but not interferon alpha (IFN-), advanced the time course of apoptosis. Furthermore, caspase 8 was activated on day 4 post-infection, the same day when caspase 3 was activated. TNF receptor 1 was induced during a late stage of TULV infection. These data suggest that, unlike during influenza A virus infection, TNF-, but not type I IFN-/, may contribute significantly to apoptosis in a synergistic manner with TULV propagation. Interestingly, pretreatment with a broad-spectrum caspase inhibitor, z-VAD-fmk, efficiently inhibited apoptosis of TULV-infected Vero E6 cells. Taken together, these results suggest that TULV replication initiates a typical apoptotic programme involving caspase 8 activation.

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2004-11-01
2020-01-23
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References

  1. Aggarwal, B. B. & Vilcek, J. (editors) ( 1992; ). Tumor necrosis factor: structure, function and mechanism of action. New York, NY: Marcel Dekker.
  2. Akhmatova, N. K., Yusupova, R. S., Khaiboullina, S. F. & Sibiryak, S. V. ( 2003; ). Lymphocyte apoptosis during hemorragic fever with renal syndrome. Russ J Immunol 8, 37–46.
    [Google Scholar]
  3. Antic, D., Wright, K. E. & Kang, C. Y. ( 1992; ). Maturation of Hantaan virus glycoproteins G1 and G2. Virology 189, 324–328.[CrossRef]
    [Google Scholar]
  4. Balachandran, S., Roberts, P. C., Kipperman, T., Bhalla, K. N., Compans, R. W., Archer, D. R. & Barber, G. N. ( 2000; ). Alpha/beta interferons potentiate virus-induced apoptosis through activation of the FADD/caspase-8 death signaling pathway. J Virol 74, 1513–1523.[CrossRef]
    [Google Scholar]
  5. Barber, G. N. ( 2001; ). Host defense, viruses and apoptosis. Cell Death Differ 8, 113–126.[CrossRef]
    [Google Scholar]
  6. Benedict, C. A., Banks, T. A. & Ware, C. F. ( 2003; ). Death and survival: viral regulation of TNF signaling pathways. Curr Opin Immunol 15, 59–65.[CrossRef]
    [Google Scholar]
  7. Budihardjo, I., Oliver, H., Lutter, M., Luo, X. & Wang, X. ( 1999; ). Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol 15, 269–290.[CrossRef]
    [Google Scholar]
  8. Chao, D. T. & Korsmeyer, S. J. ( 1998; ). Bcl-2 family: regulators of cell death. Annu Rev Immunol 16, 395–419.[CrossRef]
    [Google Scholar]
  9. Chawla-Sarkar, M., Lindner, D. J., Liu, Y. F., Williams, B. R., Sen, G. C., Silverman, R. H. & Borden, E. C. ( 2003; ). Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis. Apoptosis 8, 237–249.[CrossRef]
    [Google Scholar]
  10. Cory, S. & Adams, J. M. ( 2002; ). The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2, 647–656.[CrossRef]
    [Google Scholar]
  11. Earnshaw, W. C., Martins, L. M. & Kaufmann, S. H. ( 1999; ). Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68, 383–424.[CrossRef]
    [Google Scholar]
  12. Gavrilovskaya, I. N., Shepley, M., Shaw, R., Ginsberg, M. H. & Mackow, E. R. ( 1998; ). β 3 integrins mediate the cellular entry of hantaviruses that cause respiratory failure. Proc Natl Acad Sci U S A 95, 7074–7079.[CrossRef]
    [Google Scholar]
  13. Gavrilovskaya, I. N., Brown, E. J., Ginsberg, M. H. & Mackow, E. R. ( 1999; ). Cellular entry of hantaviruses which cause hemorrhagic fever with renal syndrome is mediated by β 3 integrins. J Virol 73, 3951–3959.
    [Google Scholar]
  14. Geimonen, E., Neff, S., Raymond, T., Kocer, S. S., Gavrilovskaya, I. N. & Mackow, E. R. ( 2002; ). Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses. Proc Natl Acad Sci U S A 99, 13837–13842.[CrossRef]
    [Google Scholar]
  15. Kanerva, M., Mustonen, J. & Vaheri, A. ( 1998; ). Pathogenesis of puumala and other hantavirus infections. Rev Med Virol 8, 67–86.[CrossRef]
    [Google Scholar]
  16. Kang, J. I., Park, S. H., Lee, P. W. & Ahn, B. Y. ( 1999; ). Apoptosis is induced by hantaviruses in cultured cells. Virology 264, 99–105.[CrossRef]
    [Google Scholar]
  17. Khaiboullina, S. F. & St Jeor, S. C. ( 2002; ). Hantavirus immunology. Viral Immunol 15, 609–625.[CrossRef]
    [Google Scholar]
  18. Kolakofsky, D. & Hacker, D. ( 1991; ). Bunyavirus RNA synthesis: genome transcription and replication. In Bunyaviruses, pp. 143–159. Edited by D. Kolakofsky & D. Hacker. Heidelberg: Springer.
  19. Li, X. D., Mäkelä, T. P., Guo, D., Soliymani, R., Koistinen, V., Vapalahti, O., Vaheri, A. & Lankinen, H. ( 2002; ). Hantavirus nucleocapsid protein interacts with the Fas-mediated apoptosis enhancer Daxx. J Gen Virol 83, 759–766.
    [Google Scholar]
  20. Linderholm, M., Ahlm, C., Settergren, B., Waage, A. & Tarnvik, A. ( 1996; ). Elevated plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-6, and IL-10 in patients with hemorrhagic fever with renal syndrome. J Infect Dis 173, 38–43.[CrossRef]
    [Google Scholar]
  21. Lowy, R. J. ( 2003; ). Influenza virus induction of apoptosis by intrinsic and extrinsic mechanisms. Int Rev Immunol 22, 425–449.[CrossRef]
    [Google Scholar]
  22. Markotic, A., Hensley, L., Geisbert, T., Spik, K. & Schmaljohn, C. ( 2003; ). Hantaviruses induce cytopathic effects and apoptosis in continuous human embryonic kidney cells. J Gen Virol 84, 2197–2202.[CrossRef]
    [Google Scholar]
  23. Melen, K., Keskinen, P., Ronni, T., Sareneva, T., Lounatmaa, K. & Julkunen, I. ( 1996; ). Human MxB protein, an interferon-alpha-inducible GTPase, contains a nuclear targeting signal and is localized in the heterochromatin region beneath the nuclear envelope. J Biol Chem 271, 23478–23486.[CrossRef]
    [Google Scholar]
  24. Meyer, B. J. & Schmaljohn, C. S. ( 2000; ). Persistent hantavirus infections: characteristics and mechanisms. Trends Microbiol 8, 61–67.[CrossRef]
    [Google Scholar]
  25. Mori, M., Rothman, A. L., Kurane, I., Montoya, J. M., Nolte, K. B., Norman, J. E., Waite, D. C., Koster, F. T. & Ennis, F. A. ( 1999; ). High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome. J Infect Dis 179, 295–302.[CrossRef]
    [Google Scholar]
  26. Nam, J. H., Hwang, K. A., Yu, C. H. & 7 other authors ( 2003; ). Expression of interferon inducible genes following Hantaan virus infection as a mechanism of resistance in A549 cells. Virus Genes 26, 31–38.[CrossRef]
    [Google Scholar]
  27. Nijhawan, D., Honarpour, N. & Wang, X. ( 2000; ). Apoptosis in neural development and disease. Annu Rev Neurosci 23, 73–87.[CrossRef]
    [Google Scholar]
  28. Oltvai, Z. N., Milliman, C. L. & Korsmeyer, S. J. ( 1993; ). Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74, 609–619.[CrossRef]
    [Google Scholar]
  29. Plyusnin, A. & Morzunov, S. P. ( 2001; ). Virus evolution and genetic diversity of hantaviruses and their rodent hosts. Curr Top Microbiol Immunol 256, 47–75.
    [Google Scholar]
  30. Plyusnin, A., Vapalahti, O. & Vaheri, A. ( 1996; ). Hantaviruses: genome structure, expression and evolution. J Gen Virol 77, 2677–2687.[CrossRef]
    [Google Scholar]
  31. Schmaljohn, C. S., Hasty, S. E., Dalrymple, J. M. & 8 other authors ( 1985; ). Antigenic and genetic properties of viruses linked to hemorrhagic fever with renal syndrome. Science 227, 1041–1044.[CrossRef]
    [Google Scholar]
  32. Schmaljohn, C. S., Schmaljohn, A. L. & Dalrymple, J. M. ( 1987; ). Hantaan virus M RNA: coding strategy, nucleotide sequence, and gene order. Virology 157, 31–39.[CrossRef]
    [Google Scholar]
  33. Strasser, A., O'Connor, L. & Dixit, V. M. ( 2000; ). Apoptosis signaling. Annu Rev Biochem 69, 217–245.[CrossRef]
    [Google Scholar]
  34. Sundstrom, J. B., McMullan, L. K., Spiropoulou, C. F., Hooper, W. C., Ansari, A. A., Peters, C. J. & Rollin, P. E. ( 2001; ). Hantavirus infection induces the expression of RANTES and IP-10 without causing increased permeability in human lung microvascular endothelial cells. J Virol 75, 6070–6085.[CrossRef]
    [Google Scholar]
  35. Tanaka, N., Sato, M., Lamphier, M. S., Nozawa, H., Oda, E., Noguchi, S., Schreiber, R. D., Tsujimoto, Y. & Taniguchi, T. ( 1998; ). Type I interferons are essential mediators of apoptotic death in virally infected cells. Genes Cells 3, 29–37.[CrossRef]
    [Google Scholar]
  36. Temonen, M., Lankinen, H., Vapalahti, O., Ronni, T., Julkunen, I. & Vaheri, A. ( 1995; ). Effect of interferon-alpha and cell differentiation on Puumala virus infection in human monocyte/macrophages. Virology 206, 8–15.[CrossRef]
    [Google Scholar]
  37. Temonen, M., Mustonen, J., Helin, H., Pasternack, A., Vaheri, A. & Holthöfer, H. ( 1996; ). Cytokines, adhesion molecules, and cellular infiltration in nephropathia epidemica kidneys: an immunohistochemical study. Clin Immunol Immunopathol 78, 47–55.[CrossRef]
    [Google Scholar]
  38. Tsujimoto, Y. & Croce, C. M. ( 1986; ). Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci U S A 83, 5214–5218.[CrossRef]
    [Google Scholar]
  39. Vapalahti, O., Kallio-Kokko, H., Närvänen, A. & 7 other authors ( 1995; ). Human B-cell epitopes of Puumala virus nucleocapsid protein, the major antigen in early serological response. J Med Virol 46, 293–303.[CrossRef]
    [Google Scholar]
  40. Vapalahti, O., Lundkvist, Å., Kukkonen, S. K. & 10 other authors ( 1996; ). Isolation and characterization of Tula virus, a distinct serotype in the genus Hantavirus, family Bunyaviridae. J Gen Virol 77, 3063–3067.[CrossRef]
    [Google Scholar]
  41. Vapalahti, O., Mustonen, J., Lundkvist, Å., Henttonen, H., Plyusnin, A. & Vaheri, A. ( 2003; ). Hantavirus infections in Europe. Lancet Infect Dis 3, 653–661.[CrossRef]
    [Google Scholar]
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