Negative regulation of MAVS-mediated innate immune response by ASC.

Abstract

Stringent control of the type I interferon signaling pathways is critical to effective host immune responses, however, the molecular mechanisms that negatively regulate these pathways are still poorly understood. Here, we show that apoptosis speck-like protein (ASC), an adaptor protein of inflammasome complex, can inhibit IFN-β signaling response by interacting with mitochondrial antiviral signaling protein (MAVS). Importantly, ASC-specific siRNA knockdown enhanced virus-induced type I interferon production, with consequent reduction of virus replication. Taken together, these results suggest that ASC, as a negative regulator of the MAVS-mediated innate immunity, may play an important role in host protection upon virus infection.