Bcl-2 and Bcl-xL overexpression inhibits cytochrome c release, activation of multiple caspases, and virus release following coxsackievirus B3 infection

Christopher M. Carthy, Bobby Yanagawa, Honglin Luo, David J. Granville, Decheng Yang, Paul Cheung, Caroline Cheung, Mitra Esfandiarei, Charles M. Rudin, Craig B. Thompson, David W C Hunt, Bruce M. McManus

Research output: Contribution to journalArticlepeer-review

Abstract

Coxsackievirus B3, a cytopathic virus in the family Picornaviridae, induces degenerative changes in host cell morphology. Here we demonstrate cytochrome c release and caspases-2, -3, -6, -7, -8, and -9 processing. Enforced Bcl-2 and Bcl-xL expression markedly reduced release of cytochrome c, presentation of the mitochondrial epitope 7A6, and depressed caspase activation following infection. In comparison, cell death using TRAIL ligand caused caspase-8 processing prior to cytochrome c release and executioner caspases and cell death was only partially rescued by Bcl-2 and Bcl-xL overexpression. Disruption of the mitochondrial inner membrane potential following CVB3 infection was not inhibited by zVAD.fmk treatment. Bcl-2 or Bcl-xL overexpression or zVAD.fmk treatment delayed the loss of host cell viability and decreased progeny virus release following infection. Our data suggest that mitochondrial release of cytochrome c may be an important early event in caspase activation in CVB3 infection, and, as such, may contribute to the loss of host-cell viability and progeny virus release.

Original languageEnglish (US)
Pages (from-to)147-157
Number of pages11
JournalVirology
Volume313
Issue number1
DOIs
StatePublished - Aug 15 2003
Externally publishedYes

Keywords

  • Apoptosis
  • Bcl-2
  • Bcl-xL
  • Caspase
  • Coxsackievirus B3
  • Cytochrome c
  • Myocarditis

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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