The RNA sensor MDA5 detects SARS-CoV-2 infection

Sci Rep. 2021 Jul 1;11(1):13638. doi: 10.1038/s41598-021-92940-3.


Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19, by producing cytokines including type I and III interferons (IFNs) and proinflammatory factors such as IL6 and TNF. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes to severe COVID-19. We studied how cells detect SARS-CoV-2 infection. We report that the cytosolic RNA sensor MDA5 was required for type I and III IFN induction in the lung cancer cell line Calu-3 upon SARS-CoV-2 infection. Type I and III IFN induction further required MAVS and IRF3. In contrast, induction of IL6 and TNF was independent of the MDA5-MAVS-IRF3 axis in this setting. We further found that SARS-CoV-2 infection inhibited the ability of cells to respond to IFNs. In sum, we identified MDA5 as a cellular sensor for SARS-CoV-2 infection that induced type I and III IFNs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / immunology*
  • Cell Line
  • Humans
  • Immunity, Innate
  • Interferon Lambda
  • Interferon Type I / immunology*
  • Interferon-Induced Helicase, IFIH1 / immunology*
  • Interferons / immunology*
  • RNA / immunology
  • SARS-CoV-2 / immunology*


  • Interferon Type I
  • RNA
  • Interferons
  • IFIH1 protein, human
  • Interferon-Induced Helicase, IFIH1
  • Interferon Lambda