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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.
  • Banerjee A; Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
  • El-Sayes N; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Budylowski P; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Jacob RA; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Richard D; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Maan H; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Aguiar JA; Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
  • Demian WL; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Baid K; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • D'Agostino MR; Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
  • Ang JC; Vector Institute for Artificial Intelligence, Toronto, ON M5G 1M1, Canada.
  • Murdza T; Peter Munk Cardiac Centre, University Health Network, Toronto, ON M5G 2C4, Canada.
  • Tremblay BJ; Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
  • Afkhami S; Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
  • Karimzadeh M; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Irving AT; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Yip L; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Ostrowski M; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Hirota JA; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Kozak R; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Capellini TD; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Miller MS; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Wang B; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Mubareka S; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • McGeer AJ; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • McArthur AG; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
  • Doxey AC; Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
  • Mossman K; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada.
iScience ; 24(5): 102477, 2021 May 21.
Article in English | MEDLINE | ID: covidwho-1201540
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.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: IScience Year: 2021 Document Type: Article Affiliation country: J.isci.2021.102477

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: IScience Year: 2021 Document Type: Article Affiliation country: J.isci.2021.102477