SARS-CoV-2 encoded microRNAs are involved in the process of virus infection and host immune response

摘要

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 in vivo 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.e.,EXOC7,RAD9A,and TFE3 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.