Autophagy triggered by MAVS inhibits Coxsackievirus A16 replication.

ABSTRACT

Mitochondrial antiviral signaling protein (MAVS), a crucial adaptor protein localized on mitochondria, plays vital roles in various biological processes. Autophagy and apoptosis are two independent and closely linked cell death pathways. But whether MAVS could induce apoptosis and autophagy in rhabdomyosarcoma cells (RD cells) and what is the relationship between autophagy and apoptosis still remains elusive. Here, we reveal that overexpression of MAVS could trigger both apoptosis and autophagy in RD cells. Interestingly, MAVS-induced apoptosis was dependent on the activation of the c-Jun N-terminal kinase (JNK) signaling pathway and inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway. Also, it was found that inhibition of autophagy by 3-methyladenine (3-MA) enhanced MAVS-induced apoptosis resulting in increased cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP). Meanwhile, autophagy induction by rapamycin resulted in decreased MAVS-induced apoptosis. In addition, we found that MAVS expression was inhibited upon Coxsackievirus A16 (CA16) infection and overexpression of MAVS could inhibit CA16 replication. Collectively, our study provides novel insights into the link between apoptosis and autophagy induced by MAVS overexpression in RD cells and gains a greater understanding of MAVS-induced antiviral functions, which provide new targets for CA16 treatment. Keywords CA16; MAVS; apoptosis; autophagy.