期刊
JOURNAL OF IMMUNOLOGY
卷 192, 期 3, 页码 1171-1183出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1300842
关键词
-
类别
资金
- Spemann Graduate School of Biology and Medicine [GSC-4]
- Centre for Biological Signalling Studies Grant [EXC-294]
- Virtual Liver Network
- German Federal Ministry of Education and Research
- National Institutes of Health [AI-093967]
Semliki Forest virus (SFV) requires RNA replication and Bax/Bak for efficient apoptosis induction. However, cells lacking Bax/Bak continue to die in a caspase-dependent manner. In this study, we show in both mouse and human cells that this Bax/Bak-independent pathway involves dsRNA-induced innate immune signaling via mitochondrial antiviral signaling (MAVS) and caspase-8. Bax/Bakdeficient or Bcl-2-or Bcl-x(L)-overexpressing cells lacking MAVS or caspase-8 expression are resistant to SFV-induced apoptosis. The signaling pathway triggered by SFV does neither involve death receptors nor the classical MAVS effectors TNFR-associated factor-2, IRF-3/7, or IFN-beta but the physical interaction of MAVS with caspase-8 on mitochondria in a FADD-independent manner. Consistently, caspase-8 and -3 activation are reduced in MAVS-deficient cells. Thus, after RNA virus infection MAVS does not only elicit a type I antiviral response but also recruits caspase-8 to mitochondria to mediate caspase-3 activation and apoptosis in a Bax/Bak-independent manner.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据