The RNA sensor MDA5 detects SARS-CoV-2 infection

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...

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Auteurs principaux: Natalia G. Sampaio, Lise Chauveau, Jonny Hertzog, Anne Bridgeman, Gerissa Fowler, Jurgen P. Moonen, Maeva Dupont, Rebecca A. Russell, Marko Noerenberg, Jan Rehwinkel
Format: article
Langue:EN
Publié: Nature Portfolio 2021
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Accès en ligne:https://doaj.org/article/bf7b2861bd4e49ec90699e30b9ce5848
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Résumé: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.