PEDV Nsp14 induces mitophagy-mediated degradation of MAVS to antagonize host innate immunity and facilitate viral proliferation

作者：Lei Yang, Qisheng Qian, Yan-Gang Sun, Xinxin Chen, Guangxu Xing, Jiaqing Zhang, Baosong Xing, Songlin Qiao, Rui Li, Gaiping Zhang · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.00498-25 · 被引用次数：7 · 研究领域：Animal Virus Infections Studies、Animal Disease Management and Epidemiology、Virus-based gene therapy research

Porcine epidemic diarrhea virus (PEDV) leads to a high mortality in neonatal piglets and causes serious harm to the global swine industry. PEDV has been shown to exploit diverse strategies for antagonism of host innate immunity and promotion of self-replication. However, the underlying mechanisms involved in PEDV immunosuppression remain to be fully elucidated. The current study reveals that PEDV triggers mitophagy to suppress host innate immune responses and facilitate viral proliferation. Mechanistically, PEDV non-structural protein (Nsp) 14 was identified to mediate the interaction between the mitophagy receptor NDP52 and mitochondrial outer membrane protein TOM20 to induce mitophagy. Subsequently, Nsp14-induced mitophagy resulted in the degradation of mitochondrial antiviral signaling protein (MAVS) to suppress interferon-β (IFN-β) production and promote viral propagation. These findings deepen the understanding of PEDV pathogenesis and provide novel targets for the development of antiviral avenues. IMPORTANCE: The global pig farming industry has suffered huge economic losses from PEDV, underscoring an urgent need for in-depth research on its pathogenesis. Host innate immunity functions as the first line of defense against PEDV propagation, and PEDV has developed multiple countermeasures to dampen host antiviral responses. Here, we found that PEDV Nsp14 induced mitophagy via mediating the interaction between NDP52 and TOM20, which led to MAVS degradation and hampered IFN-...