Sec6 suppresses BoHV-1-triggered innate immunity through NDP52-mediated autophagic degradation of STING

Sec6 is a constituent subunit of the exocyst complex, which plays a critical role in exocytosis. However, its involvement in DNA virus Infection induced-innate immune responses has remained unclear. Here, we demonstrate that Sec6 suppresses the innate immune response triggered by bovine herpesvirus 1 (BoHV-1) and promotes viral Infection. Specifically, Sec6 directly targets the STING for degradation, thereby suppressing STING-dependent innate immune signaling pathways. Mechanistically, Sec6 promotes the interaction between the selective Autophagy receptor NDP52 and STING, and facilitates the autophagic degradation of STING. Notably, knockdown of NDP52 abolishes Sec6-mediated suppression of IFN-β and interferon-stimulated genes (ISGs) production, and impairs Sec6's ability to enhance BoHV-1 replication. Collectively, these findings reveal a novel mechanism by which BoHV-1 evades host innate immunity and highlight the Sec6-NDP52-STING axis as a potential target for the development of Antiviral therapies.