Abstract
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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Acknowledgements
This work was supported by the Heilongjiang Postdoctoral fund (LBH-Z18207), the National Natural Science Foundation of China (31802198), the Fundamental Research Funds for the Provincial Universities (2018-KYYWF-0553), the National Key Research and Development Program of China (2017YFC0908001) and the Spark Research Fund from the Fourth Affiliated Hospital of Harbin Medical University (HYDSYXH201914).
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Supplement Fig 1. The promoter sequence of pri-miR-27b. The transcription start site (TSS) was C and was marked in bold.
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Wang, C., Xue, M., Wu, P. et al. Coronavirus transmissible gastroenteritis virus antagonizes the antiviral effect of the microRNA miR-27b via the IRE1 pathway. Sci. China Life Sci. 65, 1413–1429 (2022). https://doi.org/10.1007/s11427-021-1967-x
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DOI: https://doi.org/10.1007/s11427-021-1967-x