TY - JOUR T1 - The RNA sensor MDA5 detects SARS-CoV-2 infection JF - bioRxiv DO - 10.1101/2021.03.26.437180 SP - 2021.03.26.437180 AU - Natalia G. Sampaio AU - Lise Chauveau AU - Jonny Hertzog AU - Anne Bridgeman AU - Gerissa Fowler AU - Jurgen P. Moonen AU - Maeva Dupont AU - Rebecca A. Russell AU - Marko Noerenberg AU - Jan Rehwinkel Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/03/27/2021.03.26.437180.abstract N2 - 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.Competing Interest StatementThe authors have declared no competing interest. ER -