Interplay between SARS-CoV-2 and the type I interferon response

PLoS Pathog. 2020 Jul 29;16(7):e1008737. doi: 10.1371/journal.ppat.1008737. eCollection 2020 Jul.


The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. An unbalanced immune response, characterized by a weak production of type I interferons (IFN-Is) and an exacerbated release of proinflammatory cytokines, contributes to the severe forms of the disease. SARS-CoV-2 is genetically related to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused outbreaks in 2003 and 2013, respectively. Although IFN treatment gave some encouraging results against SARS-CoV and MERS-CoV in animal models, its potential as a therapeutic against COVID-19 awaits validation. Here, we describe our current knowledge of the complex interplay between SARS-CoV-2 infection and the IFN system, highlighting some of the gaps that need to be filled for a better understanding of the underlying molecular mechanisms. In addition to the conserved IFN evasion strategies that are likely shared with SARS-CoV and MERS-CoV, novel counteraction mechanisms are being discovered in SARS-CoV-2-infected cells. Since the last coronavirus epidemic, we have made considerable progress in understanding the IFN-I response, including its spatiotemporal regulation and the prominent role of plasmacytoid dendritic cells (pDCs), which are the main IFN-I-producing cells. While awaiting the results of the many clinical trials that are evaluating the efficacy of IFN-I alone or in combination with antiviral molecules, we discuss the potential benefits of a well-timed IFN-I treatment and propose strategies to boost pDC-mediated IFN responses during the early stages of viral infection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Betacoronavirus / drug effects*
  • Betacoronavirus / immunology*
  • Betacoronavirus / isolation & purification
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Humans
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology*
  • Interferon Type I / therapeutic use*
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology
  • Prognosis
  • SARS-CoV-2


  • Antiviral Agents
  • Interferon Type I

Supplementary concepts

  • COVID-19 drug treatment

Grant support

Research in the laboratory of NJ is funded by the CNRS, the Institut Pasteur, the European Molecular Biology Organisation (EMBO) Young Investigator Program, and the Agence Nationale de la Recherche Scientifique (ANR 16 CE15 0025 01 VIRO-STORM). Research related to the topic of this review in the team led by MD is supported by the Agence Nationale de la Recherche (ANR Flash COVID-19 and ANR 19-CE15-0025-01 JCJC iSYN). Research related to the topic of this review in the team led by SN is supported by the Labex EpiGenMed, an Investissements d’avenir program (ANR-10-LABX-12-01), the Région Occitanie and the Agence Nationale de la Recherche (ANR Flash COVID-19). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.