Getah virus Nsp3 binds G3BP to block formation of bona fide stress granules

文献类型： 外文期刊

第一作者： Qi, Xiaoyi

作者： Qi, Xiaoyi;Zhao, Ruihan;Yao, Xiaohui;Liu, Qinqiu;Liu, Panrao;Zhu, Zhenbang;Tu, Changchun;Li, Xiangdong;Tu, Changchun;Gong, Wenjie;Li, Xiangdong

作者机构：

关键词： Stress granules; GETV; Replication; G3BP; Nsp3

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.5； 五年影响因子：8.7 ）

ISSN： 0141-8130

年卷期： 2024 年 279 卷

页码：

收录情况： SCI

摘要： Stress granules (SGs) are cytoplasmic aggregates of proteins and mRNA that form in response to diverse environmental stressors, including viral infections. Several viruses possess the ability to block the formation of stress granules by targeting the SGs marker protein G3BP. However, the molecular functions and mechanisms underlying the regulation of SGs formation by Getah virus (GETV) remain unclear. In this study, we found that GETV infection triggered the formation of Nsp3-G3BP aggregates, which differed in composition from SGs. Further studies revealed that the presence of these aggregates was dependent on the activation of the PKR/eIF2 alpha signaling pathway. Interestingly, we found that Nsp3 HVD domain blocked the formation of SGs by binding to G3BP NTF2 domain. Moreover, knockout of G3BP in NCI-H1299 cells had no effect on GETV replication, while overexpression of G3BP to form the genuine SGs significantly inhibited GETV replication. Overall, our study elucidates a novel role GETV Nsp3 to change the composition of SG as well as cellular stress response.

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