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

High-content screening of coronavirus genes for innate immune suppression reveals enhanced potency of SARS-CoV-2 proteins

Erika J. Olson, David M. Brown, Timothy Z. Chang, Lin Ding, Tai L. Ng, H. Sloane Weiss, Yukiye Koide, Peter Koch, Nathan Rollins, Pia Mach, Tobias Meisinger, Trenton Bricken, Joshua Rollins, Yun Zhang, Colin Molloy, Yun Zhang, Bridget N. Queenan, Timothy Mitchison, Debora Marks, Jeffrey C. Way, John I. Glass, View ORCID ProfilePamela A. Silver
doi: https://doi.org/10.1101/2021.03.02.433434
Erika J. Olson
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
2Wyss Institute, Harvard University. 3 Blackfan St., Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David M. Brown
4J. Craig Venter Institute, 9605 Medical Center Drive, Suite 150, Rockville, MD 20850.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timothy Z. Chang
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
2Wyss Institute, Harvard University. 3 Blackfan St., Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lin Ding
5J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA 92037.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tai L. Ng
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
H. Sloane Weiss
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yukiye Koide
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
2Wyss Institute, Harvard University. 3 Blackfan St., Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter Koch
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathan Rollins
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pia Mach
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
2Wyss Institute, Harvard University. 3 Blackfan St., Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tobias Meisinger
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Trenton Bricken
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joshua Rollins
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yun Zhang
5J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA 92037.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Colin Molloy
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yun Zhang
5J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA 92037.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bridget N. Queenan
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timothy Mitchison
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Debora Marks
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeffrey C. Way
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
2Wyss Institute, Harvard University. 3 Blackfan St., Boston, MA 02115 USA.
3Laboratory of Systems Pharmacology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: pamela_silver@hms.harvard.edu jglass@jcvi.org jeff.way@wyss.harvard.edu
John I. Glass
5J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA 92037.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: pamela_silver@hms.harvard.edu jglass@jcvi.org jeff.way@wyss.harvard.edu
Pamela A. Silver
1Department of Systems Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
2Wyss Institute, Harvard University. 3 Blackfan St., Boston, MA 02115 USA.
3Laboratory of Systems Pharmacology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115 USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Pamela A. Silver
  • For correspondence: pamela_silver@hms.harvard.edu jglass@jcvi.org jeff.way@wyss.harvard.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Summary

Suppression of the host intracellular innate immune system is an essential aspect of viral replication. Here, we developed a suite of medium-throughput high-content cell-based assays to reveal the effect of individual coronavirus proteins on antiviral innate immune pathways. Using these assays, we screened the 196 protein products of seven coronaviruses (SARS-CoV-2, SARS-CoV-1, 229E, NL63, OC43, HKU1 and MERS). This includes a previously unidentified gene in SARS-CoV-2 encoded within the Spike gene. We observe immune-suppressing activity in both known host-suppressing genes (e.g., NSP1, Orf6, NSP3, and NSP5) as well as other coronavirus genes, including the newly identified SARS-CoV-2 protein. Moreover, the genes encoded by SARS-CoV-2 are generally more potent immune suppressors than their homologues from the other coronaviruses. This suite of pathway-based and mechanism-agnostic assays could serve as the basis for rapid in vitro prediction of the pathogenicity of novel viruses based on provision of sequence information alone.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* Co-first authors

  • ↵** Lead contact

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-ND 4.0 International license.
Back to top
PreviousNext
Posted March 02, 2021.
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.
High-content screening of coronavirus genes for innate immune suppression reveals enhanced potency of SARS-CoV-2 proteins
(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
High-content screening of coronavirus genes for innate immune suppression reveals enhanced potency of SARS-CoV-2 proteins
Erika J. Olson, David M. Brown, Timothy Z. Chang, Lin Ding, Tai L. Ng, H. Sloane Weiss, Yukiye Koide, Peter Koch, Nathan Rollins, Pia Mach, Tobias Meisinger, Trenton Bricken, Joshua Rollins, Yun Zhang, Colin Molloy, Yun Zhang, Bridget N. Queenan, Timothy Mitchison, Debora Marks, Jeffrey C. Way, John I. Glass, Pamela A. Silver
bioRxiv 2021.03.02.433434; doi: https://doi.org/10.1101/2021.03.02.433434
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
High-content screening of coronavirus genes for innate immune suppression reveals enhanced potency of SARS-CoV-2 proteins
Erika J. Olson, David M. Brown, Timothy Z. Chang, Lin Ding, Tai L. Ng, H. Sloane Weiss, Yukiye Koide, Peter Koch, Nathan Rollins, Pia Mach, Tobias Meisinger, Trenton Bricken, Joshua Rollins, Yun Zhang, Colin Molloy, Yun Zhang, Bridget N. Queenan, Timothy Mitchison, Debora Marks, Jeffrey C. Way, John I. Glass, Pamela A. Silver
bioRxiv 2021.03.02.433434; doi: https://doi.org/10.1101/2021.03.02.433434

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

  • Systems Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (2646)
  • Biochemistry (5259)
  • Bioengineering (3671)
  • Bioinformatics (15788)
  • Biophysics (7247)
  • Cancer Biology (5624)
  • Cell Biology (8088)
  • Clinical Trials (138)
  • Developmental Biology (4763)
  • Ecology (7510)
  • Epidemiology (2059)
  • Evolutionary Biology (10571)
  • Genetics (7727)
  • Genomics (10125)
  • Immunology (5187)
  • Microbiology (13896)
  • Molecular Biology (5383)
  • Neuroscience (30754)
  • Paleontology (215)
  • Pathology (876)
  • Pharmacology and Toxicology (1524)
  • Physiology (2253)
  • Plant Biology (5017)
  • Scientific Communication and Education (1040)
  • Synthetic Biology (1384)
  • Systems Biology (4145)
  • Zoology (811)