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Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape

Kevin R. McCarthy, Linda J. Rennick, Sham Nambulli, View ORCID ProfileLindsey R. Robinson-McCarthy, View ORCID ProfileWilliam G. Bain, Ghady Haidar, View ORCID ProfileW. Paul Duprex
doi: https://doi.org/10.1101/2020.11.19.389916
Kevin R. McCarthy
1Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
3Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
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  • For correspondence: krm@pitt.edu pduprex@pitt.edu
Linda J. Rennick
1Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Sham Nambulli
1Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Lindsey R. Robinson-McCarthy
4Department of Genetics, Harvard Medical School, Boston, MA, USA
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William G. Bain
5Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, UPMC, Pittsburgh, PA, USA
6Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
7VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
Roles: Staff Physician
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Ghady Haidar
8Division of Infectious Disease, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
9Division of Infectious Disease, Department of Internal Medicine, UPMC, Pittsburgh, PA, USA
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W. Paul Duprex
1Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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  • For correspondence: krm@pitt.edu pduprex@pitt.edu
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Abstract

Zoonotic pandemics, like that caused by SARS-CoV-2, can follow the spillover of animal viruses into highly susceptible human populations. Their descendants have adapted to the human host and evolved to evade immune pressure. Coronaviruses acquire substitutions more slowly than other RNA viruses, due to a proofreading polymerase. In the spike glycoprotein, we find recurrent deletions overcome this slow substitution rate. Deletion variants arise in diverse genetic and geographic backgrounds, transmit efficiently, and are present in novel lineages, including those of current global concern. They frequently occupy recurrent deletion regions (RDRs), which map to defined antibody epitopes. Deletions in RDRs confer resistance to neutralizing antibodies. By altering stretches of amino acids, deletions appear to accelerate SARS-CoV-2 antigenic evolution and may, more generally, drive adaptive evolution.

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-NC-ND 4.0 International license.
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Posted January 19, 2021.
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Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape
Kevin R. McCarthy, Linda J. Rennick, Sham Nambulli, Lindsey R. Robinson-McCarthy, William G. Bain, Ghady Haidar, W. Paul Duprex
bioRxiv 2020.11.19.389916; doi: https://doi.org/10.1101/2020.11.19.389916
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Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape
Kevin R. McCarthy, Linda J. Rennick, Sham Nambulli, Lindsey R. Robinson-McCarthy, William G. Bain, Ghady Haidar, W. Paul Duprex
bioRxiv 2020.11.19.389916; doi: https://doi.org/10.1101/2020.11.19.389916

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