Sec6 suppresses BEFV-triggered type I IFN responses by promoting P62-mediated MAVS degradation.

Sec6 is one of the eight subunits of the exocyst complex, playing a specific role in cell-cell adhesion and vesicle trafficking. However, its role in the replication of bovine ephemeral fever virus (BEFV) and the antiviral innate immune response has remains unclear. In this study, we demonstrate that Sec6 inhibits the BEFV-triggered type I IFN (IFN-I) signaling response and promotes viral replication. Further research revealed that Sec6 degrades mitochondrial antiviral signaling protein (MAVS) through the autophagy pathway. Mechanistically, Sec6 promotes the association between autophagy receptor P62 and MAVS, enhancing autophagy degradation of MAVS. Silencing Sec6 inhibits the interaction between MAVS and P62. In addition, Sec6 failed to degrade MAVS in P62-knockdown cells, resulting in the loss of its ability to suppress IFN-I signaling and enhance viral replication. This study reveals a previously unrecognized role of Sec6 in modulating the antiviral innate immunity and its impact on BEFV replication.