SUMMARY
Type I interferons (IFNs) are our first line of defence against a virus. Protein over-expression studies have suggested the ability of SARS-CoV-2 proteins to block 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 lacking. Here we demonstrate that SARS-CoV-2 infection induces a mild 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. Our data demonstrate that SARS-CoV-2 is not adept in blocking type I IFN responses and provide support for ongoing IFN clinical trials.
Competing Interest Statement
This study was supported by a Canadian Institutes of Health Research (CIHR) COVID-19 rapid response grant to principal applicant K.M. and Co-Applicants A.B., A.G.M., M.S.M. and S.M. A.B. was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC). Computer resources were in part supplied by the McMaster Service Lab and Repository computing cluster, funded in part by grants to A.G.M. from the Canadian Foundation for Innovation. J.A.H. is supported by the Canada Research Chairs Program and an Ontario Early Career Researcher Award. M.S.M. is supported by a CIHR COVID-19 rapid response grant, a CIHR New Investigator Award and an Ontario Early Researcher Award.
Footnotes
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HIGHLIGHTS
SARS-CoV-2 infection in human lung cells induces the expression of type I interferons
SARS-CoV-2 infection activates canonical transcription factors that are involved in type I interferon expression and signaling
SARS-CoV-2 cannot inhibit exogenous stimulation of type I IFN expression
SARS-CoV-2 cannot inhibit exogenous activation of type I IFN signaling
Moderate cases of COVID-19 upregulate higher serum levels of IL10 and IFNα, whereas severe cases of COVID-19 display higher serum levels of IL6, TNFα and IL8
In vitro immunoblot data and serum cytokine protein levels (Figures 2-4).