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

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, present...

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Published in:Virology (New York, N.Y.) N.Y.), 2003-08, Vol.313 (1), p.147-157
Main Authors: Carthy, Christopher M, Yanagawa, Bobby, Luo, Honglin, Granville, David J, Yang, Decheng, Cheung, Paul, Cheung, Caroline, Esfandiarei, Mitra, Rudin, Charles M, Thompson, Craig B, Hunt, David W.C, McManus, Bruce M
Format: Article
Language:English
Subjects:
Amino Acid Chloromethyl Ketones - pharmacology
Animals
Apoptosis
Bcl-2
bcl-X Protein
Bcl-xL
Caspase
Caspase 9
Caspase Inhibitors
Caspases - metabolism
Cell Line
Coxsackievirus B3
Coxsackievirus Infections - metabolism
Cytochrome c
Cytochromes c - metabolism
Enterovirus B, Human - physiology
Epitopes - metabolism
Humans
Mice
Mitochondria - metabolism
Myocarditis
Proto-Oncogene Proteins c-bcl-2 - metabolism
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Summary: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.
ISSN:0042-6822
1096-0341
DOI:10.1016/S0042-6822(03)00242-3