Seneca Valley Virus 3C Protease Inhibits Stress Granule Formation by Disrupting eIF4GI-G3BP1 Interaction.
Seneca Valley Virus 3C Protease Inhibits Stress Granule Formation by Disrupting eIF4GI-G3BP1 Interaction.
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塞内卡谷病毒 3C 蛋白酶通过破坏 eIF4GI-G3BP1 相互作用来抑制应激颗粒形成
DOI：
10.3389/fimmu.2020.577838
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发表时间：
2020
影响因子：
7.3
通讯作者：
Qian P
中科院分区：
文献类型：
--
作者：
Wen W;Zhao Q;Yin M;Qin L;Hu J;Chen H;Li X;Qian P
应激颗粒(SGS)是mRNA的储存场所，与转录调控有关，是应对各种环境胁迫和病毒感染的动态结构。塞尼卡谷病毒(Seneca Valley Virus，SVV)是一种溶瘤的核糖核酸病毒，属于短小病毒科，可引起水泡病，与口蹄疫和其他猪水泡病不同。在本研究中，我们发现SVV在感染早期以PKR-eIF2α依赖的方式诱导SG的形成，G3BP1和eIF4GI标记蛋白的募集证明了这一点。令人惊讶的是，我们发现下调SG标记蛋白TIA1或G3BP1，或表达eif2α非磷酸化突变体抑制SG的形成，但这种对瞬时SG形成的抑制对SVV的繁殖没有显著影响。G3BP1的缺失显著减弱了NF-κB信号通路的激活。此外，我们还发现，SVV在感染后期抑制了SG的形成，而3C蛋白酶是抑制SG形成所必需的，这取决于它的酶活性。此外，我们还发现，3C蛋白酶通过破坏eIF4GI-G3BP1相互作用来阻断SG的形成。总之，我们的结果表明，SVV以eIF2PKR依赖的方式诱导瞬时SG的形成，而3C蛋白酶通过干扰eIF4GI-G3BP1相互作用来抑制SG的形成。
Stress granules (SGs) are the sites of mRNA storage and related to the regulation of mRNA translation, which are dynamic structures in response to various environmental stresses and viral infections. Seneca Valley virus (SVV), an oncolytic RNA virus belonging to Picornaviridae family, can cause vesicular disease (VD) indistinguished from foot-and-mouth disease (FMD) and other pig VDs. In this study, we found that SVV induced SG formation in the early stage of infection in a PKR-eIF2α dependent manner, as demonstrated by the recruitment of marker proteins of G3BP1 and eIF4GI. Surprisingly, we found that downregulating SG marker proteins TIA1 or G3BP1, or expressing an eIF2α non-phosphorylatable mutant inhibited SG formation, but this inhibition of transient SG formation had no significant effect on SVV propagation. Depletion of G3BP1 significantly attenuated the activation of NF-κB signaling pathway. In addition, we found that SVV inhibited SG formation at the late stage of infection and 3C protease was essential for the inhibition depending on its enzyme activity. Furthermore, we also found that 3C protease blocked the SG formation by disrupting eIF4GI-G3BP1 interaction. Overall, our results demonstrate that SVV induces transient SG formation in an eIF2α phosphorylation and PKR-dependent manner, and that 3C protease inhibits SG formation by interfering eIF4GI-G3BP1 interaction.
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