SARS-CoV-2 encoded microRNAs are involved in the process of virus infection and host immune response
Zhi Liu, Jianwei Wang, Yiyue Ge, Yuyu Xu, Mengchen Guo, Kai Mi, Rui Xu, Yang Pei, Qiankun Zhang, Xiaoting Luan, Zhibin Hu, Ying Chi, Xingyin Liu
Abstract
The outbreak of COVID-19 caused by SARS-CoV-2 is spreading worldwide, with the pathogenesis mostly unclear. Both virus and host-derived microRNA (miRNA) play essential roles in the pathology of virus infection. This study aims to uncover the mechanism for SARS-CoV-2 pathogenicity from the perspective of miRNA. We scanned the SARS-CoV-2 genome for putative miRNA genes and miRNA targets and conducted <i>in vivo</i> experiments to validate the virus-encoded miRNAs and their regulatory role on the putative targets. One of such virus-encoded miRNAs, MR147-3p, was overexpressed that resulted in significantly decreased transcript levels of all of the predicted targets in human,<i> i.e.</i>, <i>EXOC7</i>, <i>RAD9A</i>, and <i>TFE3</i> in the virus-infected cells. The analysis showed that the immune response and cytoskeleton organization are two of the most notable biological processes regulated by the infection-modulated miRNAs. Additionally, the genomic mutation of SARS-CoV-2 contributed to the changed miRNA repository and targets, suggesting a possible role of miRNAs in the attenuated phenotype of SARS-CoV-2 during its evolution. This study provided a comprehensive view of the miRNA-involved regulatory system during SARS-CoV-2 infection, indicating possible antiviral therapeutics against SARS-CoV-2 through intervening miRNA regulation.