Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV

Kumari G. Lokugamage, View ORCID ProfileAdam Hage, Maren de Vries, Ana M. Valero-Jimenez, View ORCID ProfileCraig Schindewolf, Meike Dittmann, View ORCID ProfileRicardo Rajsbaum, View ORCID ProfileVineet D. Menachery
doi: https://doi.org/10.1101/2020.03.07.982264
Kumari G. Lokugamage
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adam Hage
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Adam Hage
Maren de Vries
3Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ana M. Valero-Jimenez
3Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Craig Schindewolf
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Craig Schindewolf
Meike Dittmann
3Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ricardo Rajsbaum
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA
2Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston TX, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ricardo Rajsbaum
Vineet D. Menachery
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA
2Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston TX, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Vineet D. Menachery
  • For correspondence: Vimenach@utmb.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

SARS-CoV-2, a novel coronavirus (CoV) that causes COVID-19, has recently emerged causing an ongoing outbreak of viral pneumonia around the world. While distinct from SARS-CoV, both group 2B CoVs share similar genome organization, origins to bat CoVs, and an arsenal of immune antagonists. 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 to SARS-CoV, the novel CoV is much more sensitive to IFN-I. In Vero and in Calu3 cells, SARS-CoV-2 is substantially attenuated in the context of IFN-I pretreatment, while SARS-CoV is not. In line with these findings, SARS-CoV-2 fails to counteract phosphorylation of STAT1 and expression of ISG proteins, while SARS-CoV is able to suppress both. Comparing SARS-CoV-2 and influenza A virus in human airway epithelial cultures (HAEC), we observe the absence of IFN-I stimulation by SARS-CoV-2 alone, but detect failure to counteract STAT1 phosphorylation upon IFN-I pretreatment resulting in near ablation of SARS-CoV-2 infection. Next, we evaluated IFN-I treatment post infection and found SARS-CoV-2 was sensitive even after establishing infection. Finally, we examined homology between SARS-CoV and SARS-CoV-2 in viral proteins shown to be interferon antagonists. The absence of an equivalent open reading frame (ORF) 3b and changes to ORF6 suggest the two key IFN-I antagonists may not maintain equivalent function in SARS-CoV-2. Together, the results identify key differences in susceptibility to IFN-I responses between SARS-CoV and SARS-CoV-2 that may help inform disease progression, treatment options, and animal model development.

Importance With the ongoing outbreak of COVID-19, differences between 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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • This manuscript adds additional data for pretreatment of Calu3 with IFN-I. Also compares immune stimulation/pretreatment in HAEC relative to influenza A virus Evaluates efficacy of IFN-I treatment post infection.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted July 13, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV
Kumari G. Lokugamage, Adam Hage, Maren de Vries, Ana M. Valero-Jimenez, Craig Schindewolf, Meike Dittmann, Ricardo Rajsbaum, Vineet D. Menachery
bioRxiv 2020.03.07.982264; doi: https://doi.org/10.1101/2020.03.07.982264
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV
Kumari G. Lokugamage, Adam Hage, Maren de Vries, Ana M. Valero-Jimenez, Craig Schindewolf, Meike Dittmann, Ricardo Rajsbaum, Vineet D. Menachery
bioRxiv 2020.03.07.982264; doi: https://doi.org/10.1101/2020.03.07.982264

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (2428)
  • Biochemistry (4784)
  • Bioengineering (3328)
  • Bioinformatics (14656)
  • Biophysics (6629)
  • Cancer Biology (5162)
  • Cell Biology (7417)
  • Clinical Trials (138)
  • Developmental Biology (4355)
  • Ecology (6869)
  • Epidemiology (2057)
  • Evolutionary Biology (9903)
  • Genetics (7338)
  • Genomics (9509)
  • Immunology (4545)
  • Microbiology (12657)
  • Molecular Biology (4936)
  • Neuroscience (28280)
  • Paleontology (199)
  • Pathology (804)
  • Pharmacology and Toxicology (1388)
  • Physiology (2019)
  • Plant Biology (4487)
  • Scientific Communication and Education (976)
  • Synthetic Biology (1297)
  • Systems Biology (3909)
  • Zoology (725)