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SARS-CoV-2 Nucleocapsid Protein Targets RIG-I-Like Receptor Pathways to Inhibit the Induction of Interferon Response.
Oh, Soo Jin; Shin, Ok Sarah.
  • Oh SJ; BK21 Graduate Program, Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea.
  • Shin OS; BK21 Graduate Program, Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea.
Cells ; 10(3)2021 03 02.
Article in English | MEDLINE | ID: covidwho-1125490
ABSTRACT
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(IC)]-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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Immunologic / Interferons / DEAD Box Protein 58 / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 Limits: Humans Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Immunologic / Interferons / DEAD Box Protein 58 / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 Limits: Humans Language: English Year: 2021 Document Type: Article