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

被引:100
作者
Carthy, CM
Yanagawa, B
Luo, HL
Granville, DJ
Yang, DC
Cheung, P
Cheung, C
Esfandiarei, M
Rudin, CM
Thompson, CB
Hunt, DWC
McManus, BM
机构
[1] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15213 USA
[2] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
[3] Univ British Columbia, St Pauls Hosp, ICAPTURE Ctr, Mcdonald Res Labs,Dept Pathol & Lab Med, Vancouver, BC, Canada
基金
加拿大健康研究院;
关键词
coxsackievirus B3; apoptosis; cytochrome c; caspase; Bcl-2; Bcl-xL; myocarditis;
D O I
10.1016/S0042-6822(03)00242-3
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:147 / 157
页数:11
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