The RNA sensor MDA5 detects SARS-CoV-2 infection

Natalia G Sampaio; Lise Chauveau; Jonny Hertzog; Anne Bridgeman; Gerissa Fowler; Jurgen P Moonen; Maeva Dupont; Rebecca A Russel; Marko Noerenberg; Jan Rehwinkel

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The RNA sensor MDA5 detects SARS-CoV-2 infection

Natalia G Sampaio; Lise Chauveau; Jonny Hertzog; Anne Bridgeman; Gerissa Fowler; Jurgen P Moonen; Maeva Dupont; Rebecca A Russel; Marko Noerenberg; Jan Rehwinkel.

Affiliation

Natalia G Sampaio; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Lise Chauveau; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Jonny Hertzog; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Anne Bridgeman; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Gerissa Fowler; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Jurgen P Moonen; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Maeva Dupont; The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Rebecca A Russel; The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Marko Noerenberg; Department of Biochemistry, University of Oxford, UK.
Jan Rehwinkel; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK

Preprint in English | bioRxiv | ID: ppbiorxiv-437180

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ABSTRACT

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.

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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint

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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint