MicroRNAs (miRNAs) are critical regulators of gene expression that may be used to identify the pathological pathways influenced by disease and cellular interactions. Viral miRNAs (v-miRNAs) encoded by both DNA and RNA viruses induce immune dysregulation, virus production, and disease pathogenesis. Given the absence of effective treatment and the prevalence of highly infective SARS-CoV-2 strains, improved understanding of viral-associated miRNAs could provide novel mechanistic insights into the pathogenesis of COVID-19. In this study, SARS-CoV-2 v-miRNAs were identified by deep sequencing in infected Calu-3 and Vero E6 cell lines. Among the ~0.1% small RNA sequences mapped to the SARS-CoV-2 genome, the top ten SARS-CoV-2 v-miRNAs (including three encoded by the N gene; v-miRNA-N) were selected. After initial screening of conserved v-miRNA-N-28612, which was identified in both SARS-CoV and SARS-CoV-2, its expression was shown to be positively associated with viral load in COVID-19 patients. Further in silico analysis and synthetic-mimic transfection of validated SARS-CoV-2 v-miRNAs revealed novel functional targets and associations with mechanisms of cellular metabolism and biosynthesis. Our findings support the development of v-miRNA-based biomarkers and therapeutic strategies based on improved understanding of the pathophysiology of COVID-19.
【저자키워드】 COVID-19, SARS-COV-2 infection, microRNA, cellular metabolism, host target genes, 【초록키워드】 Treatment, viruses, SARS-CoV-2, Biomarker, Pathogenesis, Gene Expression, SARS-CoV, miRNA, virus, metabolism, Prevalence, miRNAs, Viral, Viral load, pathophysiology, SARS-CoV-2 genome, RNA viruses, Therapeutic strategies, pathway, target, cellular metabolism, in silico analysis, N gene, disease, expression, MicroRNAs, Critical, Calu-3, mechanism, therapeutic strategy, COVID-19 patients, association, cell lines, Biosynthesis, deep sequencing, immune dysregulation, Vero E6, dysregulation, Support, disease pathogenesis, initial screening, pathogenesis of COVID-19, viral miRNAs, SARS-CoV-2 strains, infective, virus production, cellular interactions, RNA sequence, v-miRNAs, DNA and RNA, effective, selected, shown, identify, conserved, functional, absence, induce, mapped, the SARS-CoV-2 genome, v-miRNA, 【제목키워드】 SARS-CoV-2, Viral, metabolic, targeting,