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

Virology. 2003 Aug 15;313(1):147-57. doi: 10.1016/s0042-6822(03)00242-3.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Caspase 9
  • Caspase Inhibitors
  • Caspases / metabolism*
  • Cell Line
  • Coxsackievirus Infections / metabolism*
  • Cytochromes c / metabolism*
  • Enterovirus B, Human / physiology*
  • Epitopes / metabolism
  • Humans
  • Mice
  • Mitochondria / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • bcl-X Protein

Substances

  • Amino Acid Chloromethyl Ketones
  • BCL2L1 protein, human
  • Bcl2l1 protein, mouse
  • Caspase Inhibitors
  • Epitopes
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Cytochromes c
  • CASP9 protein, human
  • Casp9 protein, mouse
  • Caspase 9
  • Caspases