Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces severe pneumonia and is the cause of a worldwide pandemic. Coronaviruses, including SARS-CoV-2, have RNA proofreading enzymes in their genomes, resulting in fewer gene mutations than other RNA viruses. Nevertheless, variants of SARS-CoV-2 exist and may induce different symptoms; however, the factors and the impacts of these mutations are not well understood. We found that there is a bias to the mutations occurring in SARS-CoV-2 variants, with disproportionate mutation to uracil (U). These point mutations to U are mainly derived from cytosine (C), which is consistent with the substrate specificity of host RNA editing enzymes, APOBECs. We also found the point mutations which are consistent with other RNA editing enzymes, ADARs. For the C-to-U mutations, the context of the upstream uracil and downstream guanine from mutated position was found to be most prevalent. Further, the degree of increase of U in SARS-CoV-2 variants correlates with enhanced production of cytokines, such as TNF-α and IL-6, in cell lines when compared with stimulation by the ssRNA sequence of the isolated virus in Wuhan. Therefore, RNA editing is a factor for mutation bias in SARS-CoV-2 variants, which affects host inflammatory cytokines production.
【저자키워드】 immunology, Pathogenesis, 【초록키워드】 SARS-CoV-2, coronavirus, Mutation, Cytokines, IL-6, mutations, SARS-CoV-2 variant, Infection, virus, RNA, specificity, SARS-CoV-2 variants, RNA viruses, Impact, Wuhan, genomes, severe pneumonia, Enzymes, Inflammatory cytokine, TNF-α, Proofreading, Point mutation, cytosine, acute respiratory syndrome, Factor, enzyme, worldwide pandemic, sequence, uracil, cell line, ssRNA, guanine, upstream, downstream, variants of SARS-CoV-2, Host, Affect, prevalent, resulting, induce, mutated, gene mutation, 【제목키워드】 Mutation, SARS-CoV-2 variant, Inflammatory response, stimulate, Point,