A novel mitochondrial MAVS/caspase-8 platform links RNA virus-induced innate antiviral signaling to bax/bak-independent apoptosis

Souhayla El Maadidi, Laura Faletti, Birgit Berg, Christin Wenzl, Katrin Wieland, Zhijian J. Chen, Ulrich Maurer, Christoph Borner

Research output: Contribution to journalArticle

38 Scopus citations


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-xL-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-b 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 RNAvirus 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.

Original languageEnglish (US)
Pages (from-to)1171-1183
Number of pages13
JournalJournal of Immunology
Issue number3
Publication statusPublished - Feb 1 2014


ASJC Scopus subject areas

  • Immunology

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