SARS-CoV-2 triggers an MDA-5-dependent interferon response which is unable to control replication in lung epithelial cells.

Journal of Virology
A. RebendenneCaroline Goujon

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 19 (COVID-19), which ranges from mild respiratory symptoms to acute respiratory distress syndrome, and death in the most severe cases. Immune dysregulation with altered innate cytokine responses is thought to contribute to disease severity. Here, we characterized in depth host cell responses against SARS-CoV-2 in primary human airway epithelia (HAE) and immortalized cell lines. Our results demonstrate that primary HAE and model cells elicit a robust induction of type I and III interferons (IFNs). Importantly, we show for the first time that melanoma differentiation associated gene (MDA)-5 is the main sensor of SARS-CoV-2 in lung cells. IFN exposure strongly inhibited viral replication and de novo production of infectious virions. However, despite high levels of IFNs produced in response to SARS-CoV-2 infection, the IFN response was unable to control viral replication in lung cells, contrary to what was previously reported in intestinal epithelial cells. Altogether, these results highlight the complex and ambiguous interplay between viral replication and the timing of IFN responses.IMPORTANCE Mammalian cells express sensors...Continue Reading

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Citations

Apr 29, 2021·Nature Microbiology·Thomas P PeacockWendy S Barclay
Jun 12, 2021·Communications Biology·Matthieu SimeoniDavid Gatfield
Jun 16, 2021·The Journal of Experimental Medicine·Nagarjuna R CheemarlaEllen F Foxman
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Jul 9, 2021·Signal Transduction and Targeted Therapy·Lan YangYufeng Zhou
Jul 15, 2021·Journal of Virology·Da-Yuan ChenMohsan Saeed
Aug 10, 2021·International Journal of Rheumatic Diseases·Satoshi HamaYutaka Okano

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