数字农科院2.0

Bovine coronavirus Nsp14 protein promotes viral replication by degrading TRAF3 to inhibit interferon production

文献类型： 外文期刊

作者： He Sun;Yuchang Liu;Xinyu Yang;Wenzhen Qin;Xiaoxiao Lu;Yizhen Wang;Wu Tong;Hai Yu;Hao Zheng;Guangzhi Tong;Tongling Shan;Ning Kong

作者机构：

关键词： Bovine coronavirus;Degradation;Nsp14 protein;TRAF3

期刊名称： Veterinary Microbiology

ISSN： 1873-2542

年卷期： 2025 年 310 卷

页码：

收录情况： SCIE（2025版）

摘要： Bovine coronavirus (BCoV), a member of the Betacoronavirus genus, causes severe calf gastroenteritis and respiratory disease, resulting in a significant loss of livestock. Coronavirus non-structural protein 14 (nsp14) is involved in viral RNA replication and modification and subverts host immune regulatory pathways to facilitate immune evasion. In this study, we demonstrated that BCoV nsp14 mediates TNF receptor-associated factor 3 (TRAF3) degradation through the coordinated targeting of the ubiquitin-proteasome and autophagy-lysosomal pathways, thereby potentiating viral replication. During autophagic degradation, nsp14 recruits and interacts with the E3 ubiquitin ligase STUB1 to ubiquitinate the TRAF3 protein. This ubiquitinated TRAF3 is then recognized and delivered via the cargo receptor Tollip for autophagic degradation. RNA interference-mediated knockdown of STUB1 or Tollip inhibited selective autophagic flux, increased the steady-state levels of TRAF3, and prevented nsp14-mediated TRAF3 degradation. Overall, we describe a new mechanism related to BCoV-mediated IFN-β suppression to promote viral replication and provided a rationale for developing therapies that target the nsp14-TRAF3 axis.

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