Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1

文献类型： 外文期刊

第一作者： Sun, Peng

作者： Sun, Peng;Zhang, Shumin;Qin, Xiaodong;Chang, Xingni;Cui, Xiaorui;Li, Haitao;Zhang, Shuaijun;Zhang, Zhidong;Luo, Jianxun;Li, Zhiyong;Sun, Peng;Gao, Huanhuan;Wang, Penghua

作者机构：

关键词： AKT; ATF4; autophagy; EIF2S1; FMDV; HSPB1; MTOR; replication; VP2

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： 2018 年 14 卷 2 期

页码：

收录情况： SCI

摘要： Foot-and-mouth disease virus (FMDV) can result in economical destruction of cloven-hoofed animals. FMDV infection has been reported to induce macroautophagy/autophagy; however, the precise molecular mechanisms of autophagy induction and effect of FMDV capsid protein on autophagy remain unknown. In the present study, we report that FMDV infection induced a complete autophagy process in the natural host cells of FMDV, and inhibition of autophagy significantly decreased FMDV production, suggesting that FMDV-induced autophagy facilitates viral replication. We found that the EIF2S1-ATF4 pathway was activated and the AKT-MTOR signaling pathway was inhibited by FMDV infection. We also observed that ultraviolet (UV)-inactivated FMDV can induce autophagy. Importantly, our work provides the first piece of evidence that expression of FMDV capsid protein VP2 can induce autophagy through the EIF2S1-ATF4-AKT-MTOR cascade, and we found that VP2 interacted with HSPB1 (heat shock protein family B [small] member 1) and activated the EIF2S1-ATF4 pathway, resulting in autophagy and enhanced FMDV replication. In addition, we show that VP2 induced autophagy in a variety of mammalian cell lines and decreased aggregates of a model mutant HTT (huntingtin) polyglutamine expansion protein (HTT103Q). Overall, our results demonstrate that FMDV capsid protein VP2 induces autophagy through interaction with HSPB1 and activation of the EIF2S1-ATF4 pathway.

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