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

doi:10.1016/j.isci.2021.102477

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

iScience. 2021 May 21;24(5):102477. doi: 10.1016/j.isci.2021.102477. Epub 2021 Apr 26.

Authors

Arinjay Banerjee^{1

2

3}, Nader El-Sayes^{3

4}, Patrick Budylowski⁵, Rajesh Abraham Jacob^{1

2

3}, Daniel Richard⁶, Hassaan Maan^{7

8}, Jennifer A Aguiar⁹, Wael L Demian^{1

2

3}, Kaushal Baid^{3

4}, Michael R D'Agostino^{2

3

4}, Jann Catherine Ang^{2

3

4}, Tetyana Murdza^{3

4}, Benjamin J-M Tremblay⁹, Sam Afkhami^{2

3

4}, Mehran Karimzadeh⁷, Aaron T Irving^{10

11}, Lily Yip¹², Mario Ostrowski^{13

14}, Jeremy A Hirota^{2

15

16}, Robert Kozak^{12

17}, Terence D Capellini⁶, Matthew S Miller^{2

3

4}, Bo Wang^{7

8

18

17}, Samira Mubareka^{12

17}, Allison J McGeer^{19

20}, Andrew G McArthur^{2

4}, Andrew C Doxey^{2

9}, Karen Mossman^{1

2

3}

Affiliations

¹ Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
² Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada.
³ McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.
⁴ Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
⁵ Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁶ Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
⁷ Vector Institute for Artificial Intelligence, Toronto, ON M5G 1M1, Canada.
⁸ Peter Munk Cardiac Centre, University Health Network, Toronto, ON M5G 2C4, Canada.
⁹ Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
¹⁰ Zhejiang University - University of Edinburgh Institute, Haining, Zhejiang 314400, China.
¹¹ Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China.
¹² Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
¹³ Department of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada.
¹⁴ Keenan Research Centre for Biomedical Science of St. Michael's Hospital, UnityHealth, Toronto, ON M5B 1W8, Canada.
¹⁵ Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
¹⁶ Division of Respiratory Medicine, The University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
¹⁷ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
¹⁸ Department of Computer Science, University of Toronto, Toronto, ON M5S 2E4, Canada.
¹⁹ Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
²⁰ Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A1, Canada.

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.

Keywords: Immunology; Virology.