1887

Abstract

Punta Toro virus (PTV; genus , family ) causes apoptosis of hepatocytes in experimentally infected hamsters and in cultured HepG2 cells. Screening for expression of apoptosis-related genes has shown alterations in the genes for tumour necrosis factor- (TNF-) and the TNF receptor family. This study examined the roles of the TNF receptor-related extrinsic pathway and the Bcl-2 family-associated mitochondrial pathway in PTV-induced cell death. The effects of caspase inhibitors (caspIs) and TNF on cellular viability, virus replication, and morphological and biochemical changes in apoptosis were examined in HepG2 cells at different time points after infection with PTV (Adames strain). The results showed that caspIs dampened the virus-induced reduction in cellular viability, partially suppressed and delayed viral titres and antigen expression, and partially decreased the expression of apoptotic genes, caspase activities and DNA fragmentation. TNF treatment further decreased cellular viability after PTV infection and increased the level of apoptosis, whilst caspIs partially inhibited these effects. These findings indicate that TNF, caspase-8 and caspase-9 contribute to PTV-induced hepatocytic apoptosis and that additional mediators are probably also involved in this process. These mediators from different pathways correlated with one another and may be interlinked.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.2008/001644-0
2008-09-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/9/2175.html?itemId=/content/journal/jgv/10.1099/vir.0.2008/001644-0&mimeType=html&fmt=ahah

References

  1. Akhmatova N. K., Yusupova R. S., Khaiboullina S. F., Sibiryak S. V. 2003; Lymphocyte apoptosis during hemorrhagic fever with renal syndrome. Russ J Immunol 8:37–46
    [Google Scholar]
  2. Boya P., Pauleau A. L., Poncet D., Gonzalez-Polo R. A., Zamzami N., Kroemer G. 2004; Viral proteins targeting mitochondria: controlling cell death. Biochim Biophys Acta 1659178–189 [CrossRef]
    [Google Scholar]
  3. 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]
  4. Cusi M. G., Gori Savellini G., Terrosi C., Di Genova G., Valassina M., Valentini M., Bartolommei S., Miracco C. 2005; Development of a mouse model for the study of Toscana virus pathogenesis. Virology 333:66–73 [CrossRef]
    [Google Scholar]
  5. Ding X., Xu F., Chen H., Tesh R. B., Xiao S.-Y. 2005; Apoptosis of hepatocytes caused by Punta Toro virus ( Bunyaviridae : Phlebovirus ) and its implication for phlebovirus pathogenesis. Am J Pathol 167:1043–1049 [CrossRef]
    [Google Scholar]
  6. Earnshaw W. C. 1999; Apoptosis. A cellular poison cupboard. Nature 397:387–389 [CrossRef]
    [Google Scholar]
  7. Ewings K. E., Wiggins C. M., Cook S. J. 2007; Bim and the pro-survival Bcl-2 proteins: opposites attract, ERK repels. Cell Cycle 6:2236–2240 [CrossRef]
    [Google Scholar]
  8. Fisher A. F., Tesh R. B., Tonry J., Guzman H., Liu D., Xiao S.-Y. 2003; Induction of severe disease in hamsters by two sandfly fever group viruses, Punta Toro and Gabek Forest ( Phlebovirus ; Bunyaviridae ), similar to that caused by Rift Valley fever virus. Am J Trop Med Hyg 69:269–276
    [Google Scholar]
  9. Ghavami S., Hashemi M., Kadkhoda K., Alavian S. M., Bay G. H., Los M. 2005; Apoptosis in liver diseases – detection and therapeutic applications. Med Sci Monit 11:RA337–RA345
    [Google Scholar]
  10. Hatano E. 2007; Tumor necrosis factor signaling in hepatocyte apoptosis. J Gastroenterol Hepatol 22:Suppl. 1S43–S44 [CrossRef]
    [Google Scholar]
  11. 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]
  12. Klingström J., Hardestam J., Stoltz M., Zuber B., Lundkvist A., Linder S., Ahlm C. 2006; Loss of cell membrane integrity in Puumala hantavirus-infected patients correlates with levels of epithelial cell apoptosis and perforin. J Virol 80:8279–8282 [CrossRef]
    [Google Scholar]
  13. Li X. D., Kukkonen S., Vapalahti O., Plyusnin A., Lankinen H., Vaheri A. 2004; Tula hantavirus infection of Vero E6 cells induces apoptosis involving caspase 8 activation. J Gen Virol 85:3261–3268 [CrossRef]
    [Google Scholar]
  14. Li X. D., Lankinen H., Putkuri N., Vapalahti O., Vaheri A. 2005; Tula hantavirus triggers pro-apoptotic signals of ER stress in Vero E6 cells. Virology 333:180–189 [CrossRef]
    [Google Scholar]
  15. 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]
  16. 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]
  17. Nguyen M. L., Blaho J. A. 2007; Apoptosis during herpes simplex virus infection. Adv Virus Res 69:67–97
    [Google Scholar]
  18. Nichol S. T., Beaty B. J., Elliott R. M., Goldbach R., Plyusnin A., Schmaljohn C. S., Tesh R. B. 2005; Genus Phlebovirus . In Virus Taxonomy: Classification and Nomenclature of Viruses. Eighth Report of the International Committee on Taxonomy of Viruses pp 709–711Edited by Fauguet C. M., Mayo M. A., Maniloff J., Desselberger U., Ball L. A. San Diego: Elsevier Academic Press;
    [Google Scholar]
  19. Nicholson D. W., Thornberry N. A. 1997; Caspases: killer proteases. Trends Biochem Sci 22:299–306 [CrossRef]
    [Google Scholar]
  20. Rust C., Gores G. J. 2000; Apoptosis and liver disease. Am J Med 108:567–574 [CrossRef]
    [Google Scholar]
  21. Sastre J., Serviddio G., Pereda J., Minana J. B., Arduini A., Vendemiale G., Poli G., Pallardo F. V., Vina J. 2007; Mitochondrial function in liver disease. Front Biosci 12:1200–1209 [CrossRef]
    [Google Scholar]
  22. Schattenberg J. M., Galle P. R., Schuchmann M. 2006; Apoptosis in liver disease. Liver Int 26:904–911 [CrossRef]
    [Google Scholar]
  23. Shen Y., Shenk T. E. 1995; Viruses and apoptosis. Curr Opin Genet Dev 5:105–111 [CrossRef]
    [Google Scholar]
  24. Sugarman B. J., Aggarwal B. B., Hass P. E., Figari I. S., Palladino M. A. Jr, Shepard H. M. 1985; Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro. Science 230:943–945 [CrossRef]
    [Google Scholar]
  25. Temonen M., Vapalahti O., Holthofer H., Brummer-Korvenkontio M., Vaheri A., Lankinen H. 1993; Susceptibility of human cells to Puumala virus infection. J Gen Virol 74:515–518 [CrossRef]
    [Google Scholar]
  26. Tesh R. B. 1979; A method for the isolation and identification of dengue viruses, using mosquito cell cultures. Am J Trop Med Hyg 28:1053–1059
    [Google Scholar]
  27. Xiao S.-Y., Zhang H., Guzman H., Tesh R. 2001; Experimental yellow fever virus infection in golden hamster ( Mesocricetus auratus ). II. Pathology. J Infect Dis 183:1437–1444 [CrossRef]
    [Google Scholar]
  28. Xiao S.-Y., Guzman H., da Rosa A. P., Zhu H. B., Tesh R. B. 2003; Alteration of clinical outcome and histopathology of yellow fever virus infection in a hamster model by previous infection with heterologous flaviviruses. Am J Trop Med Hyg 68:695–703
    [Google Scholar]
  29. Yin X. M., Ding W. X. 2003; Death receptor activation-induced hepatocyte apoptosis and liver injury. Curr Mol Med 3:491–508 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.2008/001644-0
Loading
/content/journal/jgv/10.1099/vir.0.2008/001644-0
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