PEDV NSP8 inhibits IFN-III production induced by MAVS through downregulation of PEX13

Porcine epidemic diarrhea virus (PEDV) NSP8 is a highly conserved protein that plays a crucial role in viral replication. Investigating the functional mechanisms of NSP8 contributes to a deeper understanding of PEDV pathogenesis and supports the development of antiviral strategies against coronaviruses. In this study, we elucidate how NSP8 suppresses type Ⅲ interferon (IFN-Ⅲ) production by promoting pexophagy through the downregulation of PEX13. We demonstrate that NSP8 directly interacts with PEX13 and enhances the ubiquitination of PEX5, leading to reduced peroxisome abundance and impaired mitochondrial antiviral-signaling protein (MAVS)-mediated IFN-Ⅲ signaling. These findings suggest that NSP8 hijacks the PEX13-dependent pexophagy pathway as a means of evading host antiviral defenses. This work provides critical insights into the interplay between viral proteins and host cellular machinery and highlights the NSP8-PEX13 axis as a promising target for therapeutic interventions aimed at enhancing antiviral immunity against PEDV and related coronaviruses.