Activation and evasion of type I interferon responses by SARS-CoV-2

Nat Commun. 2020 Jul 30;11(1):3810. doi: 10.1038/s41467-020-17665-9.

Abstract

The pandemic of COVID-19 has posed an unprecedented threat to global public health. However, the interplay between the viral pathogen of COVID-19, SARS-CoV-2, and host innate immunity is poorly understood. Here we show that SARS-CoV-2 induces overt but delayed type-I interferon (IFN) responses. By screening 23 viral proteins, we find that SARS-CoV-2 NSP1, NSP3, NSP12, NSP13, NSP14, ORF3, ORF6 and M protein inhibit Sendai virus-induced IFN-β promoter activation, whereas NSP2 and S protein exert opposite effects. Further analyses suggest that ORF6 inhibits both type I IFN production and downstream signaling, and that the C-terminus region of ORF6 is critical for its antagonistic effect. Finally, we find that IFN-β treatment effectively blocks SARS-CoV-2 replication. In summary, our study shows that SARS-CoV-2 perturbs host innate immune response via both its structural and nonstructural proteins, and thus provides insights into the pathogenesis of SARS-CoV-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Betacoronavirus / genetics
  • Betacoronavirus / immunology
  • Betacoronavirus / metabolism
  • Betacoronavirus / physiology*
  • COVID-19
  • Cell Line
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology*
  • Humans
  • Immune Evasion*
  • Immunity, Innate
  • Interferon Type I / metabolism*
  • Interferon-beta / genetics
  • Interferon-beta / metabolism
  • Interferon-beta / pharmacology
  • Mutation
  • Open Reading Frames
  • Pandemics
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology*
  • Promoter Regions, Genetic
  • SARS-CoV-2
  • Signal Transduction* / drug effects
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication / drug effects

Substances

  • Interferon Type I
  • Viral Proteins
  • Interferon-beta