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Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants
The emergence of highly transmissible SARS-CoV-2 variants and vaccine breakthrough infections globally mandated the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 2.13 million SARS-CoV-2 genomes from 188 countries/territories (up to June 2021) and per...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815892/ https://www.ncbi.nlm.nih.gov/pubmed/36604461 http://dx.doi.org/10.1038/s41598-022-26646-5 |
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author | Venkatakrishnan, A. J. Anand, Praveen Lenehan, Patrick J. Ghosh, Pritha Suratekar, Rohit Silvert, Eli Pawlowski, Colin Siroha, Abhishek Chowdhury, Dibyendu Roy O’Horo, John C. Yao, Joseph D. Pritt, Bobbi S. Norgan, Andrew P. Hurt, Ryan T. Badley, Andrew D. Halamka, John Soundararajan, Venky |
author_facet | Venkatakrishnan, A. J. Anand, Praveen Lenehan, Patrick J. Ghosh, Pritha Suratekar, Rohit Silvert, Eli Pawlowski, Colin Siroha, Abhishek Chowdhury, Dibyendu Roy O’Horo, John C. Yao, Joseph D. Pritt, Bobbi S. Norgan, Andrew P. Hurt, Ryan T. Badley, Andrew D. Halamka, John Soundararajan, Venky |
author_sort | Venkatakrishnan, A. J. |
collection | PubMed |
description | The emergence of highly transmissible SARS-CoV-2 variants and vaccine breakthrough infections globally mandated the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 2.13 million SARS-CoV-2 genomes from 188 countries/territories (up to June 2021) and performed whole-genome viral sequencing from 102 COVID-19 patients, including 43 vaccine breakthrough infections. We identified 92 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a 3-month window. Deletions in the Spike protein N-terminal domain were highly enriched for these ‘surge-associated mutations’ (Odds Ratio = 14.19, 95% CI 6.15–32.75, p value = 3.41 × 10(–10)). Based on a longitudinal analysis of mutational prevalence globally, we found an expanding repertoire of Spike protein deletions proximal to an antigenic supersite in the N-terminal domain that may be one of the key contributors to the evolution of highly transmissible variants. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences from 102 patients and identified 107 unique mutations, including 78 substitutions and 29 deletions. In five patients, we identified distinct deletions between residues 85–90, which reside within a linear B cell epitope. Deletions in this region arose contemporaneously on a diverse background of variants across the globe since December 2020. Overall, our findings based on genomic-epidemiology and clinical surveillance suggest that the genomic deletion of dispensable antigenic regions in SARS-CoV-2 may contribute to the evasion of immune responses and the evolution of highly transmissible variants. |
format | Online Article Text |
id | pubmed-9815892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98158922023-01-06 Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants Venkatakrishnan, A. J. Anand, Praveen Lenehan, Patrick J. Ghosh, Pritha Suratekar, Rohit Silvert, Eli Pawlowski, Colin Siroha, Abhishek Chowdhury, Dibyendu Roy O’Horo, John C. Yao, Joseph D. Pritt, Bobbi S. Norgan, Andrew P. Hurt, Ryan T. Badley, Andrew D. Halamka, John Soundararajan, Venky Sci Rep Article The emergence of highly transmissible SARS-CoV-2 variants and vaccine breakthrough infections globally mandated the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 2.13 million SARS-CoV-2 genomes from 188 countries/territories (up to June 2021) and performed whole-genome viral sequencing from 102 COVID-19 patients, including 43 vaccine breakthrough infections. We identified 92 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a 3-month window. Deletions in the Spike protein N-terminal domain were highly enriched for these ‘surge-associated mutations’ (Odds Ratio = 14.19, 95% CI 6.15–32.75, p value = 3.41 × 10(–10)). Based on a longitudinal analysis of mutational prevalence globally, we found an expanding repertoire of Spike protein deletions proximal to an antigenic supersite in the N-terminal domain that may be one of the key contributors to the evolution of highly transmissible variants. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences from 102 patients and identified 107 unique mutations, including 78 substitutions and 29 deletions. In five patients, we identified distinct deletions between residues 85–90, which reside within a linear B cell epitope. Deletions in this region arose contemporaneously on a diverse background of variants across the globe since December 2020. Overall, our findings based on genomic-epidemiology and clinical surveillance suggest that the genomic deletion of dispensable antigenic regions in SARS-CoV-2 may contribute to the evasion of immune responses and the evolution of highly transmissible variants. Nature Publishing Group UK 2023-01-05 /pmc/articles/PMC9815892/ /pubmed/36604461 http://dx.doi.org/10.1038/s41598-022-26646-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Venkatakrishnan, A. J. Anand, Praveen Lenehan, Patrick J. Ghosh, Pritha Suratekar, Rohit Silvert, Eli Pawlowski, Colin Siroha, Abhishek Chowdhury, Dibyendu Roy O’Horo, John C. Yao, Joseph D. Pritt, Bobbi S. Norgan, Andrew P. Hurt, Ryan T. Badley, Andrew D. Halamka, John Soundararajan, Venky Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants |
title | Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants |
title_full | Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants |
title_fullStr | Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants |
title_full_unstemmed | Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants |
title_short | Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants |
title_sort | expanding repertoire of sars-cov-2 deletion mutations contributes to evolution of highly transmissible variants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815892/ https://www.ncbi.nlm.nih.gov/pubmed/36604461 http://dx.doi.org/10.1038/s41598-022-26646-5 |
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