Bcl-2 and Bcl-xL overexpression inhibits cytochrome c release, activation of multiple caspases, and virus release following coxsackievirus B3 infection
Bcl-2 and Bcl-xL overexpression inhibits cytochrome c release, activation of multiple caspases, and virus release following coxsackievirus B3 infection
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DOI：
10.1016/s0042-6822(03)00242-3
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发表时间：
2003-08-15
期刊：
影响因子：
3.7
通讯作者：
McManus, BM
中科院分区：
文献类型：
--
作者：
Carthy, CM;Yanagawa, B;McManus, BM
柯萨奇病毒B3是小核糖核酸病毒科中的一种细胞病变病毒，可诱导宿主细胞形态的退行性变化。在这里，我们展示了细胞色素c的释放和半胱天冬酶-2，-3，-6，-7，-8和-9加工。加强Bcl-2和Bcl-xL的表达显着减少细胞色素c的释放，线粒体表位7A 6的介绍，并抑制感染后的半胱天冬酶激活。相比之下，使用TRAIL配体的细胞死亡导致在细胞色素c释放之前的半胱天冬酶-8加工和执行者半胱天冬酶，并且Bcl-2和Bcl-xL过表达仅部分挽救了细胞死亡。CVB 3感染后线粒体内膜电位的破坏不受zVAD治疗的抑制。Bcl-2或Bcl-xL过表达或zVAD处理延迟了宿主细胞活力的丧失，并降低了感染后子代病毒的释放。我们的数据表明，线粒体释放的细胞色素C可能是一个重要的早期事件，在CVB 3感染的半胱天冬酶激活，因此，可能会导致宿主细胞活力和后代病毒释放的损失。(C)2003 Elsevier Science（美国）。All rights reserved.
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.