TY - JOUR
T1 - A novel mitochondrial MAVS/caspase-8 platform links RNA virus-induced innate antiviral signaling to bax/bak-independent apoptosis
AU - Maadidi, Souhayla El
AU - Faletti, Laura
AU - Berg, Birgit
AU - Wenzl, Christin
AU - Wieland, Katrin
AU - Chen, Zhijian J.
AU - Maurer, Ulrich
AU - Borner, Christoph
PY - 2014/2/1
Y1 - 2014/2/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1300842
DO - 10.4049/jimmunol.1300842
M3 - Article
C2 - 24391214
AN - SCOPUS:84893354769
SN - 0022-1767
VL - 192
SP - 1171
EP - 1183
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -