Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses
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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.
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SciScore for 10.1101/2020.06.18.158154: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:The limitation of Lu et al.’ s study with SARS-CoV and other recent studies with SARS-CoV-2 is the use of protein over-expression models to identify host response modulating capabilities of viral proteins (Gordon et al., 2020; …
SciScore for 10.1101/2020.06.18.158154: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:The limitation of Lu et al.’ s study with SARS-CoV and other recent studies with SARS-CoV-2 is the use of protein over-expression models to identify host response modulating capabilities of viral proteins (Gordon et al., 2020; Jiang et al., 2020; Lei et al., 2020; Xia et al., 2020). The lack of wildtype virus infection does not represent a realistic scenario, where the dynamics of virus replication (PAMP generation) and protein translation (modulators of type I IFN response) would affect the overall antiviral outcome. Indeed, in Lei et al’s recent study, wildtype SARS-CoV-2 infection significantly upregulated transcript levels of IFNβ and IFIT1; however, ectopic expression of individual proteins led to the identification of 8 SARS-CoV-2 proteins that could inhibit the activation of the IFNβ promoter (Lei et al., 2020). The physiological relevance of over-expressing SARS-CoV-2 proteins that can block type I IFN responses remains to be validated, but it is unlikely that SARS-CoV-2 proteins will be selectively upregulated to such high amounts during the natural course of infection, while limiting the generation of stimulatory RNA molecules during virus replication. Similarly, ectopic expression of the NS1 protein from H1N1 influenza A virus strongly inhibits type I IFN responses (Jia et al., 2010; Kochs et al., 2007); however, in contrast, infection with wildtype H1N1 virus induces a type I IFN response (Jewell et al., 2007) (see supplementary Figures S3B and S3C). Thus, the phy...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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