@article {1599640, title = {Experimental and natural evidence of SARS-CoV-2-infection-induced activation of type I interferon responses}, journal = {iScience}, volume = {24}, number = {5}, year = {2021}, month = {2021 May 21}, pages = {102477}, abstract = {Type I interferons (IFNs) are our first line of defense 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 wild-type 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.}, issn = {2589-0042}, doi = {10.1016/j.isci.2021.102477}, author = {Banerjee, Arinjay and El-Sayes, Nader and Budylowski, Patrick and Jacob, Rajesh Abraham and Richard, Daniel and Maan, Hassaan and Aguiar, Jennifer A and Demian, Wael L and Baid, Kaushal and D{\textquoteright}Agostino, Michael R and Ang, Jann Catherine and Murdza, Tetyana and Tremblay, Benjamin J-M and Afkhami, Sam and Karimzadeh, Mehran and Irving, Aaron T and Yip, Lily and Ostrowski, Mario and Hirota, Jeremy A and Kozak, Robert and Capellini, Terence D and Miller, Matthew S and Wang, Bo and Mubareka, Samira and McGeer, Allison J and McArthur, Andrew G and Doxey, Andrew C and Mossman, Karen} }