SARS-CoV-2 is sensitive to type I interferon pretreatment

Abstract:

Abstract SARS-CoV-2, a novel coronavirus (CoV), has recently emerged causing an ongoing outbreak of viral pneumonia around the world. While genetically distinct from the original SARS-CoV, both group 2B CoVs share similar genome organization and origins to coronaviruses harbored in bats. Importantly, initial guidance has used insights from SARS-CoV infection to inform treatment and public health strategies. In this report, we evaluate type-I Interferon (IFN-I) sensitivity of SARS-CoV-2 relative to the original SARS-CoV. Our results indicate that while SARS-CoV-2 maintains similar viral replication kinetics to SARS-CoV in Vero cell, the novel CoV is much more sensitive to IFN-I pretreatment. Examining transcriptional factor activation and interferon stimulated gene (ISG) induction, SARS-CoV-2 in the context of type I IFN induces phosphorylation of STAT1 and increased ISG proteins. In contrast, the original SARS-CoV has no evidence for STAT1 phosphorylation or ISG protein increases even in the presence of type I IFN pretreatment. Finally, we examined homology between SARS-CoV and SARS-CoV-2 in viral proteins shown to be interferon antagonist. The absence of open reading frame (ORF) 3b and significant changes to ORF6 suggest the two key IFN antagonists may not maintain equivalent function in SARS-CoV-2. Together, the results identify key differences in susceptibility to the IFN-I response between SARS-CoV and SARS-CoV-2. that could help inform disease progression, treatment options, and animal model development. Importance With the ongoing outbreak of COVID-19 disease, differences between the SARS-CoV-2 and the original SARS-CoV could be leveraged to inform disease progression and eventual treatment options. In addition, these findings could have key implications for animal model development as well as further research into how SARS-CoV-2 modulates the type I IFN response early during infection. Article Summary SARS-CoV-2 has similar replication kinetics to SARS-CoV, but demonstrates significant sensitivity to type I interferon treatment.

SEEK ID: https://fairdomhub.org/publications/493

DOI: 10.1101/2020.03.07.982264

Projects: COVID-19 Disease Map

Publication type: Tech report

Citation: biorxiv;2020.03.07.982264v2,[Preprint]

Date Published: 9th Mar 2020

URL: http://biorxiv.org/lookup/doi/10.1101/2020.03.07.982264

Registered Mode: imported from a bibtex file

Authors: Kumari G. Lokugamage, Adam Hage, Craig Schindewolf, Ricardo Rajsbaum, Vineet D. Menachery

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Citation
Lokugamage, K. G., Hage, A., de Vries, M., Valero-Jimenez, A. M., Schindewolf, C., Dittmann, M., Rajsbaum, R., & Menachery, V. D. (2020). Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV. In []. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.03.07.982264
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Created: 8th Apr 2020 at 22:13

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