Sindbis virus induces apoptosis through a caspase-dependent, CrmA- sensitive pathway

Victor E. Nava, Antony Rosen, Michael A. Veliuona, Rollie J. Clem, Beth Levine, J. Marie Hardwick

Research output: Contribution to journalArticle

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Abstract

Sindbis virus infection of cultured cells and of neurons in mouse brains leads to programmed cell death exhibiting the classical characteristics of apoptosis. Although the mechanism by which Sindbis virus activates the cell suicide program is not known, we demonstrate here that Sindbis virus activates caspases, a family of death-inducing proteases, resulting in cleavage of several cellular substrates. To study the role of caspases in virus-induced apoptosis, we determined the effects of specific caspase inhibitors on Sindbis virus-induced cell death. CrmA (a serpin from cowpox virus) and zVAD-FMK (N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) inhibited Sindbis virus-induced cell death, suggesting that cellular caspases facilitate apoptosis induced by Sindbis virus. Furthermore, CrmA significantly increased the rate of survival of infected mice. These inhibitors appear to protect cells by inhibiting the cellular death pathway rather than impairing virus replication or by inhibiting the nsP2 and capsid viral proteases. The specificity of CrmA indicates that the Sindbis virus- induced death pathway is similar to that induced by Fas or tumor necrosis factor alpha rather than being like the death pathway induced by DNA damage. Taken together, these data suggest a central role for caspases in Sindbis virus-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)452-459
Number of pages8
JournalJournal of Virology
Volume72
Issue number1
StatePublished - Jan 1998

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Sindbis virus
Sindbis Virus
caspases
Caspases
apoptosis
Apoptosis
death
Cell Death
cell death
Peptide Hydrolases
proteinases
Cowpox virus
Serpins
suicide
Caspase Inhibitors
capsid
Capsid
mice
Virus Diseases
Virus Replication

ASJC Scopus subject areas

  • Immunology

Cite this

Nava, V. E., Rosen, A., Veliuona, M. A., Clem, R. J., Levine, B., & Hardwick, J. M. (1998). Sindbis virus induces apoptosis through a caspase-dependent, CrmA- sensitive pathway. Journal of Virology, 72(1), 452-459.

Sindbis virus induces apoptosis through a caspase-dependent, CrmA- sensitive pathway. / Nava, Victor E.; Rosen, Antony; Veliuona, Michael A.; Clem, Rollie J.; Levine, Beth; Hardwick, J. Marie.

In: Journal of Virology, Vol. 72, No. 1, 01.1998, p. 452-459.

Research output: Contribution to journalArticle

Nava, VE, Rosen, A, Veliuona, MA, Clem, RJ, Levine, B & Hardwick, JM 1998, 'Sindbis virus induces apoptosis through a caspase-dependent, CrmA- sensitive pathway', Journal of Virology, vol. 72, no. 1, pp. 452-459.
Nava VE, Rosen A, Veliuona MA, Clem RJ, Levine B, Hardwick JM. Sindbis virus induces apoptosis through a caspase-dependent, CrmA- sensitive pathway. Journal of Virology. 1998 Jan;72(1):452-459.
Nava, Victor E. ; Rosen, Antony ; Veliuona, Michael A. ; Clem, Rollie J. ; Levine, Beth ; Hardwick, J. Marie. / Sindbis virus induces apoptosis through a caspase-dependent, CrmA- sensitive pathway. In: Journal of Virology. 1998 ; Vol. 72, No. 1. pp. 452-459.
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