SERPINB1 promotes Senecavirus A replication by degrading IKBKE and regulating the IFN pathway via autophagy.

Innate immunity and autophagy play crucial roles in regulating Senecavirus A (SVA) replication. However, the reciprocal coordination between these systems during virus infection is not understood. Our results show that SERPINB1, a member of the SERPINB family, facilitates SVA replication. Mechanistically, ectopic expression of SERPINB1 increases the degradation of IκB kinase epsilon (IKBKE) through the ubiquitin-proteasome pathway. The removal of IKBKE antagonizes the IKBKE-mediated inhibition of proliferation that normally generates an interferon response via the AKT/mTOR/BECN1 axis. We conclude that SERPINB1 promotes SVA replication by eliciting autophagy-triggered innate inhibition, suggesting that SERPINB1 is a potential therapeutic target for the control of viral infection.IMPORTANCESenecavirus A (SVA) is an emerging picornavirus associated with vesicular disease, which wide spreads around the world. It has evolved multiple strategies to evade host immune surveillance. The mechanism and pathogenesis of the virus infection remain unclear. In this study, we show that SERPINB1, a member of the SERPINB family, promotes SVA replication, and regulates both innate immunity and the autophagy pathway. SERPINB1 catalyzes K48-linked polyubiquitination of IκB kinase epsilon (IKBKE) and degrades IKBKE through the proteasome pathway. Inhibition of IKBKE expression by SERPINB1 induces autophagy to decrease type I interferon signaling, and ultimately promotes SVA proliferation. These results provide importantly the theoretical basis of SVA replication and pathogenesis. SERPINB1 could be a potential therapeutic target for the control of viral infection.