Coronavirus S protein alters dsRNA accumulation and stress granule formation through regulation of ADAR1-p150 expression

文献类型： 外文期刊

第一作者： Fan, Baochao

作者： Fan, Baochao;Li, Yupeng;Wang, Yi;Yang, Shanshan;Peng, Qi;Qian, Jiali;Wang, Chuanhong;Zhang, Xue;Xu, Hong;Liu, Shiyu;He, Wenlong;Zhang, Gege;Zhu, Xuejiao;Li, Yunchuan;Zhao, Yongxiang;Hu, Mi;Wang, Wei;Zhou, Jinzhu;Guo, Rongli;He, Kongwang;Li, Bin;Fan, Baochao;Li, Yupeng;Wang, Yi;Yang, Shanshan;Peng, Qi;Qian, Jiali;Wang, Chuanhong;Zhang, Xue;Xu, Hong;Liu, Shiyu;He, Wenlong;Zhang, Gege;Zhu, Xuejiao;Li, Yunchuan;Zhao, Yongxiang;Hu, Mi;Wang, Wei;Zhou, Jinzhu;Guo, Rongli;He, Kongwang;Li, Bin;Fan, Baochao;Yang, Shanshan;Peng, Qi;Zhu, Xuejiao;Li, Yunchuan;Zhao, Yongxiang;Hu, Mi;Wang, Wei;Zhou, Jinzhu;Guo, Rongli;He, Kongwang;Li, Bin;Fan, Baochao;Qian, Jiali;Liu, Shiyu;Li, Bin;Fan, Baochao;Fan, Baochao;Li, Bin;Li, Bin

作者机构：

期刊名称：NUCLEIC ACIDS RESEARCH （ 影响因子：13.1； 五年影响因子：16.8 ）

ISSN： 0305-1048

年卷期： 2024 年 52 卷 21 期

页码：

收录情况： SCI

摘要： The precise role of the highly variable coronavirus S protein in modulating innate immune responses remains unclear. In this study, we demonstrated that the mutant strain of swine coronavirus porcine enteric diarrhea virus induced significantly lower levels of double-stranded RNA (dsRNA) accumulation, inhibited protein kinase R (PKR) activation and suppressed stress granule (SG) formation compared with the classical strain. The 29th amino acid at N-terminus of S was identified as the key functional site for regulation of SG formation, and found that mutant S inhibited PKR phosphorylation and SG formation by upregulating adenosine deaminase acting on RNA 1 (ADAR1)-p150. Notably, the Z alpha domain of ADAR1-p150 was essential for inhibiting SG formation. Upregulation of ADAR1-p150 also reduced accumulation of dsRNA depending on its RNA editing function. Virus rescue confirmed that the mutant carrying a substitution at amino acid 29 failed to induce ADAR1-p150, leading to dsRNA accumulation, PKR activation and SG formation. Interestingly, the latest severe acute respiratory syndrome coronavirus-2 strains exhibit a novel 25PPA27 deletion at N-terminus of S that was also shown to lead to altered ADAR1-p150 expression and SG inhibition. The transcription factor TCF7L2 was identified as a player in S-mediated transcriptional enhancement of ADAR1-p150. This study is the first to clarify the crucial role of N-terminus of S in immune regulation of coronaviruses. [GRAPHICS]

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