Glycosylation of classical swine fever virus Erns is essential for binding double-stranded RNA and preventing interferon-beta induction

Host cells sense double-stranded RNA (dsRNA) produced during viral replication and initiate type I interferon (IFN-α/β) production, leading to subsequent antiviral responses. Many viruses, including classical swine fever virus (CSFV), have developed strategies for counteracting the IFN-α/β response. In this study, we explored the role of the CSFV Erns glycoprotein in the inhibition of IFN-β production induced by dsRNA [poly(IC)]. Our results demonstrated that CSFV Erns could bind to exogenous dsRNA and inhibit dsRNA-induced IFN-β production but failed to inhibit TRIF-triggered IFN-β production. Our data suggest that the inhibition of IFN-β induction occurred at the initial step of the TLR3 signaling pathway. We also showed that deglycosylation of Erns rendered it unable to bind to dsRNA, and thus unable to inhibit dsRNA-induced IFN-β production. Taken together, these results indicated that N-glycan of CSFV Erns is essential for Erns blocking of IFN-β induction.