iScience (May 2021)
Experimental and natural evidence of SARS-CoV-2-infection-induced activation of type I interferon responses
- Arinjay Banerjee,
- Nader El-Sayes,
- Patrick Budylowski,
- Rajesh Abraham Jacob,
- Daniel Richard,
- Hassaan Maan,
- Jennifer A. Aguiar,
- Wael L. Demian,
- Kaushal Baid,
- Michael R. D'Agostino,
- Jann Catherine Ang,
- Tetyana Murdza,
- Benjamin J.-M. Tremblay,
- Sam Afkhami,
- Mehran Karimzadeh,
- Aaron T. Irving,
- Lily Yip,
- Mario Ostrowski,
- Jeremy A. Hirota,
- Robert Kozak,
- Terence D. Capellini,
- Matthew S. Miller,
- Bo Wang,
- Samira Mubareka,
- Allison J. McGeer,
- Andrew G. McArthur,
- Andrew C. Doxey,
- Karen Mossman
Affiliations
- Arinjay Banerjee
- Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada; Corresponding author
- Nader El-Sayes
- McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
- Patrick Budylowski
- Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada
- Rajesh Abraham Jacob
- Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada
- Daniel Richard
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
- Hassaan Maan
- Vector Institute for Artificial Intelligence, Toronto, ON M5G 1M1, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, ON M5G 2C4, Canada
- Jennifer A. Aguiar
- Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada
- Wael L. Demian
- Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada
- Kaushal Baid
- McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
- Michael R. D'Agostino
- Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
- Jann Catherine Ang
- Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
- Tetyana Murdza
- McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
- Benjamin J.-M. Tremblay
- Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada
- Sam Afkhami
- Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
- Mehran Karimzadeh
- Vector Institute for Artificial Intelligence, Toronto, ON M5G 1M1, Canada
- Aaron T. Irving
- Zhejiang University – University of Edinburgh Institute, Haining, Zhejiang 314400, China; Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China
- Lily Yip
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada
- Mario Ostrowski
- Department of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada; Keenan Research Centre for Biomedical Science of St. Michael's Hospital, UnityHealth, Toronto, ON M5B 1W8, Canada
- Jeremy A. Hirota
- Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada; Division of Respiratory Medicine, The University of British Columbia, Vancouver, BC V5Z 1M9, Canada
- Robert Kozak
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
- Terence D. Capellini
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
- Matthew S. Miller
- Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
- Bo Wang
- Vector Institute for Artificial Intelligence, Toronto, ON M5G 1M1, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, ON M5G 2C4, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5S 2E4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
- Samira Mubareka
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
- Allison J. McGeer
- Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A1, Canada
- Andrew G. McArthur
- Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
- Andrew C. Doxey
- Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada
- Karen Mossman
- Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada; Corresponding author
- Journal volume & issue
-
Vol. 24,
no. 5
p. 102477
Abstract
Summary: 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.
