Sars-cov-2 nucleocapsid protein targets rig-i-like receptor pathways to inhibit the induction of interferon response

Soo Jin Oh, Ok Sarah Shin

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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 immu-nity. 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.

Original languageEnglish
Article number530
Pages (from-to)1-13
Number of pages13
JournalCells
Volume10
Issue number3
DOIs
Publication statusPublished - 2021 Mar
Externally publishedYes

Keywords

  • Antiviral immune response
  • Coronavirus disease 2019
  • Interferon
  • RIG-I like receptors
  • SARS-CoV-2 N protein

ASJC Scopus subject areas

  • Medicine(all)

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