Experimental and natural evidence of SARS-CoV-2-infection-induced activation of type I interferon responses

Autor: Daniel Richard, Aaron T. Irving, Wael L. Demian, Sam Afkhami, Jennifer A. Aguiar, Allison McGeer, Nader El-Sayes, Rajesh Abraham Jacob, Andrew C. Doxey, Lily Yip, Mehran Karimzadeh, Arinjay Banerjee, Karen L. Mossman, Mario A. Ostrowski, Bo Wang, Kaushal Baid, Jeremy A. Hirota, Robert A. Kozak, Andrew G. McArthur, Matthew S. Miller, Hassaan Maan, Michael R. D’Agostino, Patrick Budylowski, Jann Catherine Ang, Terence D. Capellini, Samira Mubareka, Tetyana Murdza, Benjamin J.-M. Tremblay
Rok vydání: 2020
Předmět:
Zdroj: iScience, Vol 24, Iss 5, Pp 102477-(2021)
iScience
ISSN: 2589-0042
Popis: Type I interferons (IFNs) are our first line of defence against virus infection. Recent studies have suggested the ability of SARS-CoV-2 proteins to inhibit IFN responses. Emerging data also suggest that timing and extent of IFN production is associated with manifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies into wildtype SARS-CoV-2-mediated induction and inhibition of human type I IFN responses are scarce. Here we demonstrate that SARS-CoV-2 infection induces a type I IFN response in vitro and in moderate cases of COVID-19. In vitro stimulation of type I IFN expression and signaling in human airway epithelial cells is associated with activation of canonical transcriptions factors, and SARS-CoV-2 is unable to inhibit exogenous induction of these responses. Furthermore, we show that physiological levels of IFNα detected in patients with moderate COVID-19 is sufficient to suppress SARS-CoV-2 replication in human airway cells.
Graphical Abstract
Databáze: OpenAIRE