MAVS-mediated host cell defense is inhibited by Borna disease virus.

Viruses often have strategies for preventing host cell apoptosis, which antagonizes viral replication. Borna disease virus (BDV) is a neurotropic RNA virus that establishes a non-cytolytic persistent infection. Although BDV suppresses type I Interferon (IFN) through (TANK)-binding kinase 1 (TBK-1) associated BDV P protein, it is still unclear how BDV can survive in the host cell and establish a persistent infection. Recently, it has been recognized that mitochondria-mediated apoptosis through the mitochondrial antiviral signaling protein (MAVS) and the RIG-I-like receptor (RLR) signaling pathway is a crucial component of the innate immune response. In this work we show that BDV X protein colocalizes and interacts with MAVS in the mitochondria to block programmed cell death. BDV X protein-mediated inhibition of apoptosis was independent of type I IFN production and NF-κB activity. The reduction of BDV X expression with RNA interference (RNAi) or the mutation of BDV X enhanced MAVS-induced cell death. Collectively, our data provide novel insights into how BDV X protein inhibits antiviral-associated programmed cell death, through its action of MAVS function.