Evasion of Type I Interferon by SARS-CoV-2

Hongjie Xia, Zengguo Cao, Xuping Xie, Xianwen Zhang, John Yun Chung Chen, Hualei Wang, Vineet D. Menachery, Ricardo Rajsbaum, Pei Yong Shi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and host immune response determine coronavirus disease 2019 (COVID-19), but studies evaluating viral evasion of immune response are lacking. Here, we use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. We identify two sets of viral proteins that antagonize IFN-I signaling through blocking signal transducer and activator of transcription 1 (STAT1)/STAT2 phosphorylation or nuclear translocation. Remarkably, SARS-CoV-2 nsp1 and nsp6 suppress IFN-I signaling more efficiently than SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Thus, when treated with IFN-I, a SARS-CoV-2 replicon replicates to a higher level than chimeric replicons containing nsp1 or nsp6 from SARS-CoV or MERS-CoV. Altogether, the study provides insights on SARS-CoV-2 evasion of IFN-I response and its potential impact on viral transmission and pathogenesis.

Original languageEnglish (US)
Article number108234
JournalCell Reports
Volume33
Issue number1
DOIs
StatePublished - Oct 6 2020

Keywords

  • COVID-19
  • SARS-CoV-2
  • coronavirus disease 2019
  • immune evasion
  • interferon
  • replicon
  • severe acute respiratory syndrome coronavirus 2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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