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

Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion

View ORCID ProfileGuido Papa, Donna L. Mallery, Anna Albecka, Lawrence Welch, Jérôme Cattin-Ortolá, Jakub Luptak, David Paul, Harvey T. McMahon, Ian G. Goodfellow, Andrew Carter, Sean Munro, Leo C. James
doi: https://doi.org/10.1101/2020.08.13.243303
Guido Papa
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Guido Papa
Donna L. Mallery
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna Albecka
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lawrence Welch
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jérôme Cattin-Ortolá
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jakub Luptak
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Paul
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Harvey T. McMahon
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ian G. Goodfellow
2Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew Carter
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sean Munro
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leo C. James
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: lcj@mrc-lmb.cam.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells by binding to the host cell receptor Ace2 and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2, which processes the viral Spike (S) protein to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin in order to prime S protein for TMPRSS2 processing. Here we show that CRISPR-Cas9 knockout of furin reduces, but does not prevent, the production of infectious SARS-CoV-2 virus. Comparing S processing in furin knockout cells to multibasic site mutants reveals that while loss of furin substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S protein also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin in either donor or acceptor cells reduces, but does not prevent, TMPRSS2-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin promotes both SARS-CoV-2 infectivity and cell-cell spread it is not essential, suggesting furin inhibitors will not prevent viral spread.

Competing Interest Statement

The authors have declared no competing interest.

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 4.0 International license.
Back to top
PreviousNext
Posted August 19, 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.
Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion
(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
Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion
Guido Papa, Donna L. Mallery, Anna Albecka, Lawrence Welch, Jérôme Cattin-Ortolá, Jakub Luptak, David Paul, Harvey T. McMahon, Ian G. Goodfellow, Andrew Carter, Sean Munro, Leo C. James
bioRxiv 2020.08.13.243303; doi: https://doi.org/10.1101/2020.08.13.243303
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion
Guido Papa, Donna L. Mallery, Anna Albecka, Lawrence Welch, Jérôme Cattin-Ortolá, Jakub Luptak, David Paul, Harvey T. McMahon, Ian G. Goodfellow, Andrew Carter, Sean Munro, Leo C. James
bioRxiv 2020.08.13.243303; doi: https://doi.org/10.1101/2020.08.13.243303

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 (4116)
  • Biochemistry (8820)
  • Bioengineering (6523)
  • Bioinformatics (23470)
  • Biophysics (11798)
  • Cancer Biology (9216)
  • Cell Biology (13327)
  • Clinical Trials (138)
  • Developmental Biology (7440)
  • Ecology (11417)
  • Epidemiology (2066)
  • Evolutionary Biology (15160)
  • Genetics (10442)
  • Genomics (14051)
  • Immunology (9176)
  • Microbiology (22170)
  • Molecular Biology (8817)
  • Neuroscience (47600)
  • Paleontology (350)
  • Pathology (1429)
  • Pharmacology and Toxicology (2492)
  • Physiology (3733)
  • Plant Biology (8084)
  • Scientific Communication and Education (1437)
  • Synthetic Biology (2221)
  • Systems Biology (6039)
  • Zoology (1254)