Yang Lei, Qian Qisheng, Sun Yan-Gang, Chen Xin-Xin, Xing Guangxu, Zhang Jia-Qing, Xing Bao-Song, Qiao Songlin, Li Rui, Zhang Gaiping
College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, China.
Institute for Animal Health, Henan Academy of Agricultural Sciences, Zhengzhou, Henan, China.
J Virol. 2025 Aug 19;99(8):e0049825. doi: 10.1128/jvi.00498-25. Epub 2025 Jul 9.
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.
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-β production. Therefore, our work unveils a novel mechanism by which PEDV antagonizes host innate immunity to facilitate its proliferation and is beneficial for the prevention and control of the virus.
猪流行性腹泻病毒（PEDV）导致新生仔猪高死亡率，并对全球养猪业造成严重危害。已证明PEDV采用多种策略来对抗宿主固有免疫并促进自身复制。然而，PEDV免疫抑制所涉及的潜在机制仍有待充分阐明。当前研究表明，PEDV触发线粒体自噬以抑制宿主固有免疫反应并促进病毒增殖。机制上，已确定PEDV非结构蛋白（Nsp）14介导线粒体自噬受体NDP52与线粒体外膜蛋白TOM20之间的相互作用以诱导线粒体自噬。随后，Nsp14诱导的线粒体自噬导致线粒体抗病毒信号蛋白（MAVS）降解，从而抑制干扰素-β（IFN-β）产生并促进病毒传播。这些发现加深了对PEDV发病机制的理解，并为抗病毒途径的开发提供了新靶点。
全球养猪业因PEDV遭受了巨大经济损失，凸显了对其发病机制进行深入研究的迫切需求。宿主固有免疫作为抵御PEDV传播的第一道防线，而PEDV已制定多种对策来抑制宿主抗病毒反应。在此，我们发现PEDV Nsp14通过介导NDP52与TOM20之间的相互作用诱导线粒体自噬，这导致MAVS降解并阻碍IFN-β产生。因此，我们的工作揭示了PEDV对抗宿主固有免疫以促进其增殖的新机制，有利于该病毒的防控。
