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: |
0301 basic medicine
Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses Science Immunology 02 engineering and technology Biology Article Virus In vitro stimulation 03 medical and health sciences Interferon Virology medicine skin and connective tissue diseases Multidisciplinary Infection induced fungi Wild type 021001 nanoscience & nanotechnology In vitro 3. Good health respiratory tract diseases body regions 030104 developmental biology 0210 nano-technology medicine.drug |
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 |
Externí odkaz: |