Point mutation bias in SARS-CoV-2 variants results in increased ability to stimulate inflammatory responses

• Published in: Scientific reports 2020-10, Vol.10 (1), p.17766-17766, Article 17766
• Main Authors: Kosuge, Masato, Furusawa-Nishii, Emi, Ito, Koyu, Saito, Yoshiro, Ogasawara, Kouetsu
• Format: Article
• Language: English
• Subjects: 631/250; 692/420; Adenosine Deaminase - metabolism; APOBEC Deaminases - metabolism; Betacoronavirus - classification; Betacoronavirus - genetics; Betacoronavirus - immunology; Betacoronavirus - isolation & purification; Cell Line, Tumor; Coronavirus Infections - immunology; Coronavirus Infections - pathology; Coronavirus Infections - virology; COVID-19; Humanities and Social Sciences; Humans; Interleukin-6 - metabolism; multidisciplinary; Pandemics; Phylogeny; Pneumonia, Viral - immunology; Pneumonia, Viral - pathology; Pneumonia, Viral - virology; Point Mutation; RNA Editing; SARS-CoV-2; Science; Science (multidisciplinary); Tumor Necrosis Factor-alpha - metabolism; Uracil - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-74843-x

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.