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The RNA sensor MDA5 detects SARS-CoV-2 infection

2021; Nature Portfolio; Volume: 11; Issue: 1 Linguagem: Inglês

10.1038/s41598-021-92940-3

2045-2322

Natália G. Sampaio, Lise Chauveau, Jonny Hertzog, Anne Bridgeman, Gerissa Fowler, Jurgen P. Moonen, Maeva Dupont, Rebecca A. Russell, Marko Noerenberg, Jan Rehwinkel,

RNA regulation and disease

Abstract 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.