A Novel Mitochondrial MAVS/Caspase-8 Platform Links RNA Virus-Induced Innate Antiviral Signaling to Bax/Bak-Independent Apoptosis


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/Bak-deficient 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-β 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.


Projects: No Projects

J. Immunol.
J. Immunol. 192(3): 1171-83
3rd Jan 2014

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

help Authors

[Laura Faletti] [Christoph Borner]

help Attributions


help Scales

Not Specified
Views: 1577
  • Created: 22nd Jan 2014 at 15:15

Related items


Log in / Register

Need an account?
Sign up

Forgotten password?

Front Page

Virtual Liver Network


Related Projects and friends

Imprint Taverna workflow workbench myExperiment JWS Online ISATAB myGrid Sabio-RK BioPortal Semantic SBML

Powered by:


Silk icons 1.3
Crystal Clear icons

Virtual Liver Seek uses one essential cookie to keep you session open and one cookie to keep your consent.

By continuing to use this site you agree to the use of cookies