Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) that has resulted in the current pandemic. The lack of highly efficacious antiviral drugs that can manage this ongoing global emergency gives urgency to establishing a comprehensive understanding of the molecular pathogenesis of SARS-CoV-2. We characterized the role of the nucleocapsid protein (N) of SARS-CoV-2 in modulating antiviral immunity. Overexpression of SARS-CoV-2 N resulted in the attenuation of retinoic acid inducible gene-I (RIG-I)-like receptor-mediated interferon (IFN) production and IFN-induced gene expression. Similar to the SARS-CoV-1 N protein, SARS-CoV-2 N suppressed the interaction between tripartate motif protein 25 (TRIM25) and RIG-I. Furthermore, SARS-CoV-2 N inhibited polyinosinic: polycytidylic acid [poly(I:C)]-mediated IFN signaling at the level of Tank-binding kinase 1 (TBK1) and interfered with the association between TBK1 and interferon regulatory factor 3 (IRF3), subsequently preventing the nuclear translocation of IRF3. We further found that both type I and III IFN production induced by either the influenza virus lacking the nonstructural protein 1 or the Zika virus were suppressed by the SARS-CoV-2 N protein. Our findings provide insights into the molecular function of the SARS-CoV-2 N protein with respect to counteracting the host antiviral immune response.
【저자키워드】 Coronavirus disease 2019, interferon, SARS-CoV-2 N protein, antiviral immune response, RIG-I like receptors, 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, coronavirus, pandemic, Gene Expression, Influenza virus, IFN signaling, SARS-CoV-1, antiviral drug, nucleocapsid protein, Protein, N protein, IRF3, IFN, RIG-I, molecular, antiviral immunity, association, Interaction, nonstructural protein 1, acute respiratory syndrome, Zika virus, interferon regulatory factor, TBK1, type I, nuclear translocation, urgency, SARS-CoV-2 N, motif, TRIM25, pathogenesis of SARS-CoV-2, Host, lack, inhibited, characterized, suppressed, modulating, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, response, target, induction,