A novel mitochondrial MAVS/Caspase-8 platform links RNA virus-induced innate antiviral signaling to Bax/Bak-independent apoptosis
03.01.2014
El Maadidi S, Faletti L, Berg B, Wenzl C, Wieland K, Chen ZJ, Maurer U, Borner C.
J Immunol. 2014;192(3):1171-83
We show that the RNA virus Semliki Forest (SFV) induces a novel Bax/Bak-independent apoptosis pathway that involves dsRNA innate immune signaling via mitochondrial antiviral signaling (MAVS) and caspase-8. After its activation by the helicase MDA-5, MAVS recruits cytosolic caspase-8 to mitochondria and forms a new death inducing signaling complex (DISC) that activates caspase-3 and apoptosis in a death receptor- and FADD-independent manner. This novel pathway may help RNA viruses to kill cells which are usually protected by Bcl-2 overexpression, including many cancer cells.
