biostudies-literatureUnknown16(12)Lou JPorcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus that causes severe intestinal disease in piglets, employs sophisticated strategies to subvert host antiviral immunity. While type III interferons (IFN-III) play a pivotal role in mucosal defense at intestinal epithelial barriers, the mechanisms underlying PEDV evasion of IFN-III signaling remain poorly understood. Given that peroxisomes serve as critical platforms for IFN-III signaling and that their abundance influences immune activation, we investigated the role of pexophagy in PEDV-mediated immune evasion. We demonstrated that the PEDV nonstructural protein NSP8 functions as a potent inhibitor of mitochondrial antiviral-signaling protein (MAVS)-dependent IFN-III production. Functional analyses revealed that NSP8 sigmBioe0239625https://www.ebi.ac.uk/biostudies/studies/S-EPMC12691671biostudies-literaturePEDV NSP8 inhibits IFN-III production induced by MAVS through downregulation of PEX13.PMC12691671Yang ZZhu HWang XLou JJiang PLiu GfalsePEDV NSP8 inhibits IFN-III production induced by MAVS through downregulation of PEX13.Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus that causes severe intestinal disease in piglets, employs sophisticated strategies to subvert host antiviral immunity. While type III interferons (IFN-III) play a pivotal role in mucosal defense at intestinal epithelial barriers, the mechanisms underlying PEDV evasion of IFN-III signaling remain poorly understood. Given that peroxisomes serve as critical platforms for IFN-III signaling and that their abundance influences immune activation, we investigated the role of pexophagy in PEDV-mediated immune evasion. We demonstrated that the PEDV nonstructural protein NSP8 functions as a potent inhibitor of mitochondrial antiviral-signaling protein (MAVS)-dependent IFN-III production. Functional analyses revealed that NSP8 sig2025-01-01T00:00:00Z2025 Dec2026-06-07T04:58:44.409Z2026-06-07T03:07:35.095ZS-EPMC126916714118641610.1128/mbio.02396-25