POLM inhibits porcine epidemic diarrhea virus replication by degrading multiple viral structural proteins.

IF 4 2区 医学 Q2 VIROLOGY
Journal of Virology Pub Date : 2025-03-18 Epub Date: 2025-02-10 DOI:10.1128/jvi.02278-24
Xinyu Cao, Yingyu Liu, Wu Tong, Wenzhen Qin, Xinyu Yang, Hai Yu, Hao Zheng, Wen Zhang, Guangzhi Tong, Ning Kong, Tongling Shan
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引用次数: 0

Abstract

Porcine epidemic diarrhea, as a porcine epidemic diarrhea virus (PEDV)-induced infectious intestinal condition typified by diarrhea, emesis, dehydration, and anorexia, leads to death rates as high as 100% among suckling piglets. Given the existing commercial vaccines, it is essential to study host-virus interactions and formulate efficient anti-viral regimes. This study concerned a host factor POLM (a DNA polymerase family member) that exerts an anti-viral effect against PEDV proliferation. Our results indicated that POLM expression was increased following PEDV infection and was regulated by the transcription factor FOXA1. In addition, our findings indicated that POLM targeted and degraded PEDV structural proteins (N, S2, and M) by the autophagy pathway to inhibit PEDV proliferation. POLM could recruit the E3 ubiquitination ligase MARCH8 for N, S2, and M protein ubiquitination, which was subsequently recognized by p62, a cargo receptor, for translocation to the autophagic lysosome, therefore degrading the N, S2, and M proteins and preventing PEDV proliferation. In summary, we showed a novel therapeutic target for combating PEDV, i.e., using the POLM-MARCH8-p62-autophagosome pathway to degrade the PEDV N, S2, and M proteins.IMPORTANCEPEDV is a coronavirus that causes high mortality in piglets, which poses significant economic damage to swine farming. During PEDV infection, the host cells may promote the natural anti-viral immune response to suppress viral replication through a variety of potential host factors. In this study, we found upregulation of a host factor POLM by FOXA1 (a transcription factor) during PEDV infection. It was indicated that POLM could be a new anti-viral protein against the PEDV replication, which interacted with MARCH8 (an E3 ubiquitin ligase) and p62 (a cargo receptor) to facilitate the PEDV N, S2, and M protein degradation via the autophagy process. Apart from elucidating a previously unidentified anti-viral function of POLM, this study also provides a novel perspective for studying host anti-viral factors that act as regulators of anti-PEDV protein degrading pathways.

POLM通过降解多种病毒结构蛋白抑制猪流行性腹泻病毒复制。
猪流行性腹泻是猪流行性腹泻病毒(PEDV)引起的一种以腹泻、呕吐、脱水、厌食为主要表现的感染性肠道疾病,在哺乳仔猪中死亡率高达100%。鉴于现有的商业疫苗,研究宿主-病毒相互作用并制定有效的抗病毒机制至关重要。本研究涉及宿主因子POLM (DNA聚合酶家族成员)对PEDV增殖具有抗病毒作用。结果表明,PEDV感染后,POLM的表达增加,并受转录因子FOXA1的调控。此外,我们的研究结果表明,POLM通过自噬途径靶向并降解PEDV结构蛋白(N、S2和M),抑制PEDV的增殖。POLM可以招募E3泛素化连接酶MARCH8进行N、S2和M蛋白泛素化,随后被货物受体p62识别并易位到自噬溶酶体上,从而降解N、S2和M蛋白并阻止PEDV增殖。总之,我们发现了一种新的抗PEDV的治疗靶点,即使用polm - march8 -p62-自噬体途径降解PEDV的N、S2和M蛋白。pedv是一种冠状病毒,可导致仔猪高死亡率,对养猪业造成重大经济损失。在PEDV感染过程中,宿主细胞可能通过多种潜在宿主因子促进天然的抗病毒免疫反应,抑制病毒复制。在这项研究中,我们发现在PEDV感染期间FOXA1(一种转录因子)的宿主因子POLM上调。结果表明,POLM可能是一种新的抗PEDV复制的抗病毒蛋白,它与E3泛素连接酶MARCH8和货物受体p62相互作用,通过自噬过程促进PEDV N、S2和M蛋白的降解。除了阐明POLM先前未被发现的抗病毒功能外,本研究还为研究宿主抗病毒因子作为抗pedv蛋白降解途径的调节因子提供了一个新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Virology
Journal of Virology 医学-病毒学
CiteScore
10.10
自引率
7.40%
发文量
906
审稿时长
1 months
期刊介绍: Journal of Virology (JVI) explores the nature of the viruses of animals, archaea, bacteria, fungi, plants, and protozoa. We welcome papers on virion structure and assembly, viral genome replication and regulation of gene expression, genetic diversity and evolution, virus-cell interactions, cellular responses to infection, transformation and oncogenesis, gene delivery, viral pathogenesis and immunity, and vaccines and antiviral agents.
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