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SERPINB1 promotes Senecavirus A replication by degrading IKBKE and regulating the IFN pathway via autophagy
Junfang Yan1, Yanni Gao1, Juan Bai1,2
1Key Laboratory of Animal Diseases Diagnostic and Immunology, MOE International Joint Collaborative Research Laboratory for Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University , Nanjing, Jiangsu, China.
Importance:
Senecavirus 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.
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