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

Banerjee, Arinjay; El-Sayes, Nader; Budylowski, Patrick; Jacob, Rajesh Abraham; Richard, Daniel; Maan, Hassaan; Aguiar, Jennifer A.; Demian, Wael L.; Baid, Kaushal; D’Agostino, Michael R.; Ang, Jann Catherine; Murdza, Tetyana; Tremblay, Benjamin J.-M.; Afkhami, Sam; Karimzadeh, Mehran; Irving, Aaron T.; Yip, Lily; Ostrowski, Mario; Hirota, Jeremy A.; Kozak, Robert; Capellini, Terence D.; Miller, Matthew S.; Wang, Bo; Mubareka, Samira; McGeer, Allison J.; McArthur, Andrew G.; Doxey, Andrew C.; Mossman, Karen

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.