Abstract
It is urgent and important to understand the relationship of the widespread severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) with host immune response and study the underlining molecular mechanism. N 6 -methylation of adenosine (m6A) in RNA regulates many physiological and disease processes. Here, we investigate m6A modification of the SARS-CoV-2 gene in regulating the host cell innate immune response. Our data show that the SARS-CoV-2 virus has m6A modifications that are enriched in the 3′ end of the viral genome. We find that depletion of the host cell m6A methyltransferase METTL3 decreases m6A levels in SARS-CoV-2 and host genes, and m6A reduction in viral RNA increases RIG-I binding and subsequently enhances the downstream innate immune signaling pathway and inflammatory gene expression. METTL3 expression is reduced and inflammatory genes are induced in patients with severe coronavirus disease 2019 (COVID-19). These findings will aid in the understanding of COVID-19 pathogenesis and the design of future studies regulating innate immunity for COVID-19 treatment.
Keywords: METTL3; RIG-I; SARS-CoV-2; host innate immunity; inflammation; m(6)A RNA modification.
【저자키워드】 SARS-CoV-2, Inflammation, RIG-I, METTL3, host innate immunity, m(6)A RNA modification., 【초록키워드】 COVID-19, Treatment, coronavirus disease, RNA modification, Coronavirus disease 2019, coronavirus, Gene Expression, innate immune response, Innate immunity, SARS-CoV-2 virus, molecular mechanism, RNA, COVID-19 treatment, COVID-19 pathogenesis, Host immune response, methyltransferase, Patient, clade, RIG-I, Viral RNA, signaling pathway, disease, expression, adenosine, binding, innate immune, Inflammatory, METTL3, host innate immunity, regulate, viral genome, physiological, host cell, acute respiratory syndrome, acute respiratory syndrome coronavirus, severe coronavirus disease, host genes, Modification, inflammatory genes, downstream, Host, widespread, decrease, ENhance, reduced, increase, reduction in, inflammatory gene, the SARS-CoV-2, the SARS-CoV-2 virus, 【제목키워드】 innate immune response, SARS-COV-2 infection, regulate,