Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1.
Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1.
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口蹄疫病毒衣壳蛋白VP2激活细胞EIF2S1-ATF4通路并通过HSPB1诱导自噬
DOI：
10.1080/15548627.2017.1405187
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发表时间：
2018
期刊：
影响因子：
13.3
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Sun P;Zhang S;Qin X;Chang X;Cui X;Li H;Zhang S;Gao H;Wang P;Zhang Z;Luo J;Li Z
摘要口蹄疫病毒（FMDV）可导致偶蹄类动物的经济损失。已有报道FMDV感染可诱导巨自噬/自噬;然而，自噬诱导的精确分子机制和FMDV衣壳蛋白对自噬的影响仍不清楚。在本研究中，我们报告说，口蹄疫病毒感染诱导一个完整的自噬过程中的自然宿主细胞的口蹄疫病毒，自噬的抑制显着降低口蹄疫病毒的生产，这表明口蹄疫病毒诱导的自噬有利于病毒复制。我们发现FMDV感染激活了EIF 2S 1-ATF 4信号通路，抑制了AKT-MTOR信号通路。我们还观察到，紫外线（UV）灭活的口蹄疫病毒可以诱导自噬。重要的是，我们的工作提供了FMDV衣壳蛋白VP 2的表达可以通过EIF 2S 1-ATF 4-AKT-MTOR级联诱导自噬的第一个证据，并且我们发现VP 2与HSPB 1（热休克蛋白家族B [小]成员1）相互作用并激活EIF 2S 1-ATF 4通路，导致自噬和增强FMDV复制。此外，我们表明，VP 2诱导自噬在各种哺乳动物细胞系和模型突变HTT（亨廷顿）聚谷氨酰胺扩增蛋白（HTT 103 Q）的聚集体减少。总之，我们的研究结果表明，口蹄疫病毒衣壳蛋白VP 2诱导自噬通过与热休克蛋白B1和激活EIF 2S 1-ATF 4途径的相互作用。
ABSTRACT 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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影响因子：
21.3
作者：
通讯作者：
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影响因子：
6.6
作者：
Bruening, Ansgar;Rahmeh, Martina;Friese, Klaus
通讯作者：
Friese, Klaus
DOI：
10.1016/j.meegid.2008.11.005
发表时间：
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Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
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作者：
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