Interferon-Inducible Oligoadenylate Synthetase-Like Protein Acts As An Antiviral Effector Against Classical Swine Fever Virus Via The MDA5-Mediated Type ? Interferon-Signaling Pathway

Classical swine fever virus(CSFV)is the causative agent of classical swine fever(CSF),which poses a serious threat to the global pig industry.Interferon(IFN)and IFN-stimulated genes(ISGs)play a key role in host antiviral defense,which are the first line of defense against viral infection.CSFV infection triggers the type I IFN signaling pathway,resulting in the transcription of hundreds of ISGs and then ISGs exert the anti-CSFV activities.We have previously screened the porcine 2'-5'-oligoadenylate synthase-like protein(pOASL)as a potential anti-CSFV ISG using a reporter CSFV However,the mechanism of pOASL anti-CSFV activity is unknown.This study aimed to clarify the underlying antiviral mechanism of pOASL against CSFV.We confirmed that CSFV replication was significantly suppressed in lentivirus-delivered,pOASL-overexpressing PK-15 cells,whereas silencing the expression of endogenous pOASL by small interfering RNAs markedly enhanced CSFV growth.In addition,the transcriptional level of pOASL was upregulated both in vitro and in vivo upon CSFV infection.Interestingly,the anti-CSFV effects of pOASL are independent of the canonical RNase L pathway but depend on the activation of the type I IFN response.Glutathione S-transferase pulldown and coimmunoprecipitation assays revealed that pOASL interacts with MDA5,a double-stranded RNA sensor,and further enhances MDA5-mediated type I IFN signaling.Moreover,we showed that pOASL exerts anti-CSFV effects in an MDA5-dependent manner.In conclusion,pOASL is an anti-CSFV ISG,and pOASL suppresses CSFV replication via the MDA5-mediated type I IFN-signaling pathway.