SEC10 suppresses KLF15-mediated transcriptional activation of JAK1 and promotes BoHV-1 replication

SEC10 (EXOC5), a central subunit of the exocyst complex, plays a critical role in vesicle trafficking. However, its function in bovine herpesvirus 1 (BoHV-1) triggered-antiviral innate immunity and viral replication remains unclear. In this study, we identify SEC10 as a key negative regulator of antiviral immune responses. SEC10 suppresses the transcriptional expression of JAK1, thereby significantly impairing activation of the JAK-STAT signaling pathway, dampening type I interferon (IFN-I)-mediated antiviral immunity, and promoting BoHV-1 replication. Mechanistically, SEC10 downregulates the expression of the transcription factor KLF15 and subsequently modulates JAK1 transcription in a KLF15-dependent manner, establishing a "SEC10-KLF15-JAK1" regulatory axis. Collectively, our findings not only reveal SEC10 as a novel immunomodulatory factor but also uncover a previously unrecognized KLF15-dependent transcriptional mechanism that fine-tunes innate immune responses. This work provides new insights into the complex regulatory network of the JAK-STAT signaling pathway and identifies a potential therapeutic target for combating BoHV-1 infection.