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

Arinjay Banerjee, Patrick Budylowski, Daniel Richard, Hassaan Maan, Jennifer A. Aguiar, Nader El-Sayes, Michael R. D’Agostino, Benjamin J.-M. Tremblay, Sam Afkhami, Mehran Karimzadeh, Lily Yip, Mario Ostrowski, Jeremy A. Hirota, Robert Kozak, Terence D. Capellini, Matthew S. Miller, Andrew G. McArthur, Bo Wang, Andrew C. Doxey, Samira Mubareka, & Karen Mossman

bioRxiv doi:10.1101/2020.06.18.158154

Two highly pathogenic human coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have evolved proteins that can inhibit host antiviral responses, likely contributing to disease progression and high case-fatality rates. SARS-CoV-2 emerged in December 2019 resulting in a global pandemic. Recent studies have shown that SARS-CoV-2 is unable to induce a robust type I interferon (IFN) response in human cells, leading to speculation about the ability of SARS-CoV-2 to inhibit innate antiviral responses. However, innate antiviral responses are dynamic in nature and gene expression levels rapidly change within minutes to hours. In this study, we have performed a time series RNA-seq and selective immunoblot analysis of SARS-CoV-2 infected lung (Calu-3) cells to characterize early virus-host processes. SARS-CoV-2 infection upregulated transcripts for type I IFNs and interferon stimulated genes (ISGs) after 12 hours. Furthermore, we analyzed the ability of SARS-CoV-2 to inhibit type I IFN production and downstream antiviral signaling in human cells. Using exogenous stimuli, we discovered that SARS-CoV-2 is unable to modulate IFNβ production and downstream expression of ISGs, such as IRF7 and IFIT1. Thus, data from our study indicate that SARS-CoV-2 may have evolved additional mechanisms, such as masking of viral nucleic acid sensing by host cells to mount a dampened innate antiviral response. Further studies are required to fully identify the range of immune-modulatory strategies of SARS-CoV-2.

 

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