Nuclear ribonucleoprotein RALY targets virus nucleocapsid protein and induces autophagy to restrict porcine epidemic diarrhea virus replication

核糖核蛋白RALY靶向病毒核衣壳蛋白并诱导自噬以限制猪流行性腹泻病毒复制

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作者:Wenzhen Qin, Ning Kong, Yu Zhang, Sujie Dong, Huanjie Zhai, Xueying Zhai, Xinyu Yang, Chenqian Ye, Manqing Ye, Changlong Liu, Lingxue Yu, Hao Zheng, Hai Yu, Wen Zhang, Guangzhi Tong, Daoliang Lan, Wu Tong, Tongling Shan

Abstract

Porcine epidemic diarrhea virus (PEDV) causes diarrhea and dehydration in pigs and leads to great economic losses in the commercial swine industry. However, the underlying molecular mechanisms of host response to viral infection remain unclear. In the present study, we investigated a novel mechanism by which RALY, a member of the heterogeneous nuclear ribonucleoprotein family, significantly promotes the degradation of the PEDV nucleocapsid (N) protein to inhibit viral replication. Furthermore, we identified an interaction between RALY and the E3 ubiquitin ligase MARCH8 (membrane-associated RING-CH 8), as well as the cargo receptor NDP52 (nuclear dot protein 52 kDa), suggesting that RALY could suppress PEDV replication by degrading the viral N protein through a RALY-MARCH8-NDP52-autophagosome pathway. Collectively, these results suggest a preventive role of RALY against PEDV infection via the autophagy pathway and open up the possibility of inducing RALY in vivo as an effective prophylactic and preventive treatment for PEDV infection.

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