Coronavirus transmissible gastroenteritis virus antagonizes the antiviral effect of the microRNA miR-27b via the IRE1 pathway

文献类型： 外文期刊

第一作者： Xue, Mei

作者： Xue, Mei;Liu, Pinghuang;Feng, Li;Wang, Changlin;Wu, Peng;Wang, Honglei;Liu, Zhongqing;Wu, Guangzheng;Wang, Keliang;Xu, Wanhai;Wang, Changlin;Wu, Peng;Wang, Honglei;Liu, Zhongqing;Wu, Guangzheng;Wang, Keliang;Xu, Wanhai

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关键词： coronavirus; transmissible gastroenteritis coronavirus (TGEV); microRNA; inositol-requiring enzyme 1 (IRE1); immune evasion

期刊名称：SCIENCE CHINA-LIFE SCIENCES （ 影响因子：6.038； 五年影响因子：4.754 ）

ISSN： 1674-7305

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收录情况： SCI

摘要： Although the functional parameters of microRNAs (miRNAs) have been explored to some extent, the roles of these molecules in coronavirus infection and the regulatory mechanism of miRNAs in virus infection are still unclear. Transmissible gastroenteritis virus (TGEV) is an enteropathgenic coronavirus and causes high morbidity and mortality in suckling piglets. Here, we demonstrated that microRNA-27b-3p (miR-27b-3p) suppressed TGEV replication by directly targeting porcine suppressor of cytokine signaling 6 (SOCS6), while TGEV infection downregulated miR-27b-3p expression in swine testicular (ST) cells and in piglets. Mechanistically, the decrease of miR-27b-3p expression during TGEV infection was mediated by the activated inositol-requiring enzyme 1 (IRE1) pathway of the endoplasmic reticulum (ER) stress. Further studies showed that when ER stress was induced by TGEV, IRE1 acted as an RNase activated by autophosphorylation and unconventionally spliced mRNA encoding a potent transcription factor, X-box-binding protein 1 (Xbp1s). Xbp1s inhibited the transcription of miR-27 and ultimately reduced the production of miR-27b-3p. Therefore, our findings indicate that TGEV inhibits the expression of an anti-coronavirus microRNA through the IRE1 pathway and suggest a novel way in which coronavirus regulates the host cell response to infection.

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