OASL suppresses infectious bursal disease virus replication by degrading viral protein VP2 through autophagy way
Infectious bursal disease (IBD) is an acute and fatal immunosuppressive disease caused by infectious bursal disease virus (IBDV). As the obligate intracellular parasite, IBDV induction was strictly regulated by host factors. The antiviral activity and possible mechanism of host factors might provide the theoretical basis for the prevention and control of IBD. In this study, many upregulated expressed host factors induced by IBDV infection were investigated using RNA-seq screening, among which the expression levels of OASL (2,5-oligadenylate synthetase like protein) was significantly upregulated. OASL overexpression significantly inhibited IBDV replication, whereas OASL knockdown promoted IBDV replication. Interestingly, our results discovered the antiviral ability of OASL was independent of its classical enzymatic activity, which targeted viral protein VP2 for degradation, depending on the autophagy receptor p62/SQSTM1 in the autophagy pathway. Additionally, the 316 lysine (K) of VP2 is the key site for autophagy degradation, and its replacement with arginine disrupts VP2 degradation and enhanced IBDV replication. Importantly, our results firstly provided a unique and potent defense mechanism of OASL against dsRNA virus by interacting with viral protein for degradation.