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Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring

The appearance of multiple new SARS-CoV-2 variants during the COVID-19 pandemic is a matter of grave concern. Some of these variants, such as B.1.617.2, B.1.1.7, and B.1.351, manifest higher infectivity and virulence than the earlier SARS-CoV-2 variants, with potential dramatic effects on the course...

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Autores principales: Garushyants, Sofya K., Rogozin, Igor B., Koonin, Eugene V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632935/
https://www.ncbi.nlm.nih.gov/pubmed/34848826
http://dx.doi.org/10.1038/s42003-021-02858-9
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author Garushyants, Sofya K.
Rogozin, Igor B.
Koonin, Eugene V.
author_facet Garushyants, Sofya K.
Rogozin, Igor B.
Koonin, Eugene V.
author_sort Garushyants, Sofya K.
collection PubMed
description The appearance of multiple new SARS-CoV-2 variants during the COVID-19 pandemic is a matter of grave concern. Some of these variants, such as B.1.617.2, B.1.1.7, and B.1.351, manifest higher infectivity and virulence than the earlier SARS-CoV-2 variants, with potential dramatic effects on the course of the pandemic. So far, analysis of new SARS-CoV-2 variants focused primarily on nucleotide substitutions and short deletions that are readily identifiable by comparison to consensus genome sequences. In contrast, insertions have largely escaped the attention of researchers although the furin site insert in the Spike (S) protein is thought to be a determinant of SARS-CoV-2 virulence. Here, we identify 346 unique inserts of different lengths in SARS-CoV-2 genomes and present evidence that these inserts reflect actual virus variance rather than sequencing artifacts. Two principal mechanisms appear to account for the inserts in the SARS-CoV-2 genomes, polymerase slippage and template switch that might be associated with the synthesis of subgenomic RNAs. At least three inserts in the N-terminal domain of the S protein are predicted to lead to escape from neutralizing antibodies, whereas other inserts might result in escape from T-cell immunity. Thus, inserts in the S protein can affect its antigenic properties and merit monitoring.
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spelling pubmed-86329352021-12-15 Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring Garushyants, Sofya K. Rogozin, Igor B. Koonin, Eugene V. Commun Biol Article The appearance of multiple new SARS-CoV-2 variants during the COVID-19 pandemic is a matter of grave concern. Some of these variants, such as B.1.617.2, B.1.1.7, and B.1.351, manifest higher infectivity and virulence than the earlier SARS-CoV-2 variants, with potential dramatic effects on the course of the pandemic. So far, analysis of new SARS-CoV-2 variants focused primarily on nucleotide substitutions and short deletions that are readily identifiable by comparison to consensus genome sequences. In contrast, insertions have largely escaped the attention of researchers although the furin site insert in the Spike (S) protein is thought to be a determinant of SARS-CoV-2 virulence. Here, we identify 346 unique inserts of different lengths in SARS-CoV-2 genomes and present evidence that these inserts reflect actual virus variance rather than sequencing artifacts. Two principal mechanisms appear to account for the inserts in the SARS-CoV-2 genomes, polymerase slippage and template switch that might be associated with the synthesis of subgenomic RNAs. At least three inserts in the N-terminal domain of the S protein are predicted to lead to escape from neutralizing antibodies, whereas other inserts might result in escape from T-cell immunity. Thus, inserts in the S protein can affect its antigenic properties and merit monitoring. Nature Publishing Group UK 2021-11-30 /pmc/articles/PMC8632935/ /pubmed/34848826 http://dx.doi.org/10.1038/s42003-021-02858-9 Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Garushyants, Sofya K.
Rogozin, Igor B.
Koonin, Eugene V.
Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring
title Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring
title_full Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring
title_fullStr Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring
title_full_unstemmed Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring
title_short Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring
title_sort template switching and duplications in sars-cov-2 genomes give rise to insertion variants that merit monitoring
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632935/
https://www.ncbi.nlm.nih.gov/pubmed/34848826
http://dx.doi.org/10.1038/s42003-021-02858-9
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