The RNA sensor MDA5 detects SARS-CoV-2 infection

• Published in: Scientific reports Vol. 11; no. 1; p. 13638
• Main Authors: Sampaio, Natalia G., Chauveau, Lise, Hertzog, Jonny, Bridgeman, Anne, Fowler, Gerissa, Moonen, Jurgen P., Dupont, Maeva, Russell, Rebecca A., Noerenberg, Marko, Rehwinkel, Jan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-07-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/255/2514; 631/250/262/2106; 631/326/596/2553; 631/326/596/4130; Cell Line; Coronaviruses; COVID-19; COVID-19 - immunology; Humanities and Social Sciences; Humans; Immunity, Innate; Infections; Inflammation; Interferon; Interferon regulatory factor 3; Interferon Type I - immunology; Interferon-Induced Helicase, IFIH1 - immunology; Interferons - immunology; Interleukin 6; Lung cancer; multidisciplinary; RNA - immunology; SARS-CoV-2 - immunology; Science; Science (multidisciplinary); Sensors; Severe acute respiratory syndrome coronavirus 2
• ISSN: 2045-2322; 2045-2322
• 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.