BST2 suppresses porcine epidemic diarrhea virus replication by targeting and degrading virus nucleocapsid protein with selective autophagy

文献类型： 外文期刊

第一作者： Kong, Ning

作者： Kong, Ning;Shan, Tongling;Wang, Hua;Jiao, Yajuan;Zuo, Yewen;Li, Liwei;Tong, Wu;Yu, Lingxue;Jiang, Yifeng;Zhou, Yanjun;Li, Guoxin;Gao, Fei;Yu, Hai;Zheng, Hao;Tong, Guangzhi;Kong, Ning;Shan, Tongling;Li, Liwei;Tong, Wu;Yu, Lingxue;Jiang, Yifeng;Zhou, Yanjun;Li, Guoxin;Gao, Fei;Yu, Hai;Zheng, Hao;Tong, Guangzhi

作者机构：

关键词： BST2; CALCOCO2; NDP52; IRF1; MARCHF8; MARCH8; nucleocapsid protein; PEDV; replication; selective autophagy

期刊名称：AUTOPHAGY （ 影响因子：16.016； 五年影响因子：16.586 ）

ISSN： 1554-8627

年卷期：

页码：

收录情况： SCI

摘要： Interferon-induced BST2 (bone marrow stromal cell antigen 2) inhibits viral replication by tethering enveloped virions to the cell surface to restrict viral release and by inducing the NFKB-dependent antiviral immune response. However, the mechanism by which BST2 uses the selective autophagy pathway to inhibit viral replication is poorly understood. In this study, we showed that BST2 expression was significantly increased during porcine epidemic diarrhea virus (PEDV) infection of Vero cells by IRF1 targeting its promoter. We also showed that BST2 suppressed PEDV replication by binding and degrading the PEDV-encoded nucleocapsid (N) protein. The downregulation of N protein was blocked by macroautophagy/autophagy inhibitors but not a proteasome inhibitor, implying that the N protein was degraded via the selective autophagy pathway. Both the BST2 and N protein interacted with the E3 ubiquitin ligase MARCHF8/MARCH8 and the cargo receptor CALCOCO2/NDP52, and the ubiquitination of N protein was necessary for the degradation of N mediated by the BST2-MARCHF8 axis. The knockdown of MARCHF8 or ATG5 with small interfering RNAs blocked the selective autophagy pathway, rescued the protein abundance of PEDV N in 293T cells, and prevented the inhibition of PEDV replication by BST2 in Vero cells. Together, our data demonstrate the novel mechanism of BST2-mediated virus restriction, in which BST2 recruits MARCHF8 to catalyze the ubiquitination of the PEDV N protein. The ubiquitinated N protein is then recognized by CALCOCO2/NDP52, which delivers it to autolysosome for degradation through the selective autophagy pathway.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序