SARS-CoV-2 Triggers an MDA-5-Dependent Interferon Response Which Is Unable To Control Replication in Lung Epithelial Cells
Antoine Rebendenne, Ana Luiza Chaves Valadão, Marine Tauziet, Ghizlane Maarifi, Boris Bonaventure, Joe McKellar, Rémi Planès, Sébastien Nisole, Mary Arnaud‐Arnould, Olivier Moncorgé, Caroline Goujon
Abstract
Mammalian cells express sensors able to detect specific features of pathogens and induce the interferon response, which is one of the first line of defenses against viruses and help controlling viral replication. The mechanisms and impact of SARS-CoV-2 sensing in lung epithelial cells remained to be deciphered. In this study, we report that despite a high production of type I and III interferons specifically induced by MDA-5-mediated sensing of SARS-CoV-2, primary and immortalized lung epithelial cells are unable to control viral replication. However, exogenous interferons potently inhibited replication, if provided early upon viral exposure. A better understanding of the ambiguous interplay between the interferon response and SARS-CoV-2 replication is essential to guide future therapeutical interventions.