Abstract SARS‐CoV‐2 infection results in impaired interferon response in patients with severe COVID‐19. However, how SARS‐CoV‐2 interferes with host immune responses is incompletely understood. Here, we sequence small RNAs from SARS‐CoV‐2‐infected human cells and identify a microRNA (miRNA) derived from a recently evolved region of the viral genome. We show that the virus‐derived miRNA produces two miRNA isoforms in infected cells by the enzyme Dicer, which are loaded into Argonaute proteins. Moreover, the predominant miRNA isoform targets the 3′UTR of interferon‐stimulated genes and represses their expression in a miRNA‐like fashion. Finally, the two viral miRNA isoforms were detected in nasopharyngeal swabs from COVID‐19 patients. We propose that SARS‐CoV‐2 can potentially employ a virus‐derived miRNA to hijack the host miRNA machinery, which could help to evade the interferon‐mediated immune response. SARS‐CoV‐2 produces two miRNAs derived from a conserved stem‐loop structure of the ORF‐7a transcript in a Dicer‐dependent manner. These virus‐derived miRNAs interact with host Argonaute and can repress host innate immune response genes in cultured cells.
【저자키워드】 COVID‐19, SARS‐CoV‐2, miRNA, Microbiology, Virology & Host Pathogen Interaction, RNA Biology, Argonaute, interferon response, 【초록키워드】 immune response, innate immune response, microRNA, miRNA, interferon, Proteins, COVID‐19, SARS‐CoV‐2, Nasopharyngeal swab, miRNAs, Viral, Host immune response, nasopharyngeal swabs, immune responses, Patient, Dicer, immune response genes, small RNA, target, expression, Argonaute, 3′UTR, viral genome, Small RNAs, COVID‐19 patients, enzyme, infected cells, sequence, cultured cells, help, host immune responses, SARS‐CoV‐2 infection, host miRNA, infected cell, human cell, transcript, isoform, Host, identify, conserved, interfere, evade, predominant, represse, repress, SARS‐CoV‐2‐infected, viral miRNA, 【제목키워드】 microRNA, target, immune response gene,