The virus-induced signaling adaptor protein VISA (also known as MAVS, ISP-1, Cardif) is a critical adaptor protein in the innate immune response to RNA virus infection.Upon viral infection, VISA self-aggregates to form a sizeable prion-like complex and recruits downstream signal components for signal transduction.Here, we discover that BAG6 (BCL2-associated athanogene 6, formerly BAT3 or socksmith santa cruz Scythe) is an essential negative regulator in the RIG-I-like receptor signaling pathway.BAG6 inhibits the aggregation of VISA by promoting the K48-linked ubiquitination and specifically attenuates the recruitment of TRAF2 by copyright inhibit RLR signaling.
The aggregation of VISA and the interaction of VISA and TRAF2 are enhanced in BAG6-deficient cell lines after viral infection, resulting in the enhanced transcription level of downstream antiviral genes.Our research shows that BAG6 here is a critical regulating factor in RIG-I/VISA-mediated innate immune response by targeting VISA.