SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?

Introduction: SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical of a different clade. Methods: Here we use high resolution ultra-deep sequencing to analyze SARS-CoV-2 mutant spectra. Results: In 6 out of 11 SARS-CoV-2 isolat...

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Autores: Martínez-González, Brenda, Soria, Maria Eugenia, Mínguez, Pablo, Lorenzo Redondo, Ramón, Salar Vidal, Llanos, López García, Alberto, Esteban Muñoz, Mario, Durán Pastor, Antoni, Somovilla Crespo, Pilar, García Crespo, Carlos, Ávila, Ana Isabel de, Gomez, Jordi, Esteban Moreno, Jaime, Fernández Roblas, Ricardo, Gadea Gironés, Ignacio, Domingo, Esteban , Perales, Celia
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/718222
Acceso en línea:http://hdl.handle.net/10486/718222
https://dx.doi.org/10.3389/fmicb.2024.1358258
Access Level:acceso abierto
Palabra clave:COVID-19
ultra-deep sequencing
variant of concern
viral emergence
viral quasispecies
clade-discordant residues
Biología y Biomedicina / Biología
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network_name_str España
repository_id_str
dc.title.none.fl_str_mv SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?
title SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?
spellingShingle SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?
Martínez-González, Brenda
COVID-19
ultra-deep sequencing
variant of concern
viral emergence
viral quasispecies
clade-discordant residues
Biología y Biomedicina / Biología
title_short SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?
title_full SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?
title_fullStr SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?
title_full_unstemmed SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?
title_sort SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?
dc.creator.none.fl_str_mv Martínez-González, Brenda
Soria, Maria Eugenia
Mínguez, Pablo
Lorenzo Redondo, Ramón
Salar Vidal, Llanos
López García, Alberto
Esteban Muñoz, Mario
Durán Pastor, Antoni
Somovilla Crespo, Pilar
García Crespo, Carlos
Ávila, Ana Isabel de
Gomez, Jordi
Esteban Moreno, Jaime
Fernández Roblas, Ricardo
Gadea Gironés, Ignacio
Domingo, Esteban 
Perales, Celia
author Martínez-González, Brenda
author_facet Martínez-González, Brenda
Soria, Maria Eugenia
Mínguez, Pablo
Lorenzo Redondo, Ramón
Salar Vidal, Llanos
López García, Alberto
Esteban Muñoz, Mario
Durán Pastor, Antoni
Somovilla Crespo, Pilar
García Crespo, Carlos
Ávila, Ana Isabel de
Gomez, Jordi
Esteban Moreno, Jaime
Fernández Roblas, Ricardo
Gadea Gironés, Ignacio
Domingo, Esteban 
Perales, Celia
author_role author
author2 Soria, Maria Eugenia
Mínguez, Pablo
Lorenzo Redondo, Ramón
Salar Vidal, Llanos
López García, Alberto
Esteban Muñoz, Mario
Durán Pastor, Antoni
Somovilla Crespo, Pilar
García Crespo, Carlos
Ávila, Ana Isabel de
Gomez, Jordi
Esteban Moreno, Jaime
Fernández Roblas, Ricardo
Gadea Gironés, Ignacio
Domingo, Esteban 
Perales, Celia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv COVID-19
ultra-deep sequencing
variant of concern
viral emergence
viral quasispecies
clade-discordant residues
Biología y Biomedicina / Biología
topic COVID-19
ultra-deep sequencing
variant of concern
viral emergence
viral quasispecies
clade-discordant residues
Biología y Biomedicina / Biología
description Introduction: SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical of a different clade. Methods: Here we use high resolution ultra-deep sequencing to analyze SARS-CoV-2 mutant spectra. Results: In 6 out of 11 SARS-CoV-2 isolates from COVID-19 patients, the mutant spectrum of the spike (S)-coding region included two or more amino acids or deletions, that correspond to discordant viral clades. A similar observation is reported for laboratory populations of SARS-CoV-2 USA-WA1/2020, following a cell culture infection in the presence of remdesivir, ribavirin or their combinations. Moreover, some of the clade-discordant genome residues are found in the same haplotype within an amplicon. Discussion: We evaluate possible interpretations of these findings, and reviewed precedents for rapid selection of genomes with multiple mutations in RNA viruses. These considerations suggest that intra-host evolution may be sufficient to generate minority sequences which are closely related to sequences typical of other clades. The results provide a model for the origin of variants of concern during epidemic spread─in particular Omicron lineages─that does not require prolonged infection, involvement of immunocompromised individuals, or participation of intermediate, non-human hosts
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-03-14
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/718222
https://dx.doi.org/10.3389/fmicb.2024.1358258
url http://hdl.handle.net/10486/718222
https://dx.doi.org/10.3389/fmicb.2024.1358258
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?Martínez-González, BrendaSoria, Maria EugeniaMínguez, PabloLorenzo Redondo, RamónSalar Vidal, LlanosLópez García, AlbertoEsteban Muñoz, MarioDurán Pastor, AntoniSomovilla Crespo, PilarGarcía Crespo, CarlosÁvila, Ana Isabel deGomez, JordiEsteban Moreno, JaimeFernández Roblas, RicardoGadea Gironés, IgnacioDomingo, Esteban Perales, CeliaCOVID-19ultra-deep sequencingvariant of concernviral emergenceviral quasispeciesclade-discordant residuesBiología y Biomedicina / BiologíaIntroduction: SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical of a different clade. Methods: Here we use high resolution ultra-deep sequencing to analyze SARS-CoV-2 mutant spectra. Results: In 6 out of 11 SARS-CoV-2 isolates from COVID-19 patients, the mutant spectrum of the spike (S)-coding region included two or more amino acids or deletions, that correspond to discordant viral clades. A similar observation is reported for laboratory populations of SARS-CoV-2 USA-WA1/2020, following a cell culture infection in the presence of remdesivir, ribavirin or their combinations. Moreover, some of the clade-discordant genome residues are found in the same haplotype within an amplicon. Discussion: We evaluate possible interpretations of these findings, and reviewed precedents for rapid selection of genomes with multiple mutations in RNA viruses. These considerations suggest that intra-host evolution may be sufficient to generate minority sequences which are closely related to sequences typical of other clades. The results provide a model for the origin of variants of concern during epidemic spread─in particular Omicron lineages─that does not require prolonged infection, involvement of immunocompromised individuals, or participation of intermediate, non-human hostsThe author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by the Spanish Ministry of Science and Innovation, grants PID2020-113888RB-I00/AEI/10.13039/501100011033 and 202220 I116 and by the European Commission-Next Generation EU (regulation EU 2020/2024) through the CSIC’s Global Health Platform (PTI Salud Global). The work was also funded by grants PI21/00139 funding from Instituto de Salud Carlos III (ISCIII), co-funded by the European Union, CSIC-COV19-014 from Consejo Superior de Investigaciones Científicas (CSIC) and project 525/C/2021 from Fundació La Marató de TV3, grants 202136-30 and 202136-31. We also acknowledge the project S2018/BAA-4370 (PLATESA2 from Comunidad de Madrid/FEDER). Institutional grants from the Fundación Ramón Areces and Banco Santander to the CBMSO are also acknowledged. The team at CBMSO belongs to the Global Virus Network (GVN). BM-G is supported by predoctoral contract PFIS FI19/00119 from Instituto de Salud Carlos III cofinanced by Fondo Social Europeo (FSE), “El FSE invierte en tu futuro.” PM is supported by the Miguel Servet program of the Instituto de Salud Carlos III (CPII21/00015), cofinanced by the European Regional Development Fund (ERDF). AD-P is supported by the contract 13-2022-008566 cofinanced by the Comunidad de Madrid, through the Programa Investigo, en el marco del Plan de Recuperación, Transformación y Resiliencia, financed by the European Union - Next Generation EU. PS is supported by postdoctoral contract Margarita Salas, CA1/RSUE/2021 from MCIU. CG-C is supported by predoctoral contract PRE2018-083422 from MCIUFrontiers Media SADepartamento de Biología MolecularFacultad de Ciencias20242024-03-14research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/718222https://dx.doi.org/10.3389/fmicb.2024.1358258reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7182222026-06-23T12:46:27Z
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