Early temporal dynamics of cellular responses to SARS-CoV-2

Banerjee, A.; Budylowski, P.; Richard, D.; Maan, H.; Aguiar, J.; El-Sayes, N.; D'Agostino, M. R.; Tremblay, B. J.- M.; Afkhami, S.; Karimzadeh, M.; Yip, L.; Ostrowski, M. A.; Hirota, J. A.; Kozak, R.; Capellini, T. D.; Miller, M. S.; McArthur, A. G.; Wang, B.; Doxey, A. C.; Mubareka, S.; Mossman, K.

doi:10.1101/2020.06.18.158154

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bioRxiv · 10.1101/2020.06.18.158154

Early temporal dynamics of cellular responses to SARS-CoV-2

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Abstract

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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/158154v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@193c540org.highwire.dtl.DTLVardef@7b106forg.highwire.dtl.DTLVardef@1741cfforg.highwire.dtl.DTLVardef@1bde68_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL SUMMARY C_FIG

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Banerjee, A., Budylowski, P., Richard, D., Maan, H., Aguiar, J., El-Sayes, N., D'Agostino, M. R., Tremblay, B. J.- M., Afkhami, S., Karimzadeh, M., Yip, L., Ostrowski, M. A., Hirota, J. A., Kozak, R., Capellini, T. D., Miller, M. S., McArthur, A. G., Wang, B., Doxey, A. C., Mubareka, S., Mossman, K.. 2020-06-18. Early temporal dynamics of cellular responses to SARS-CoV-2. https://doi.org/10.1101/2020.06.18.158154

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