RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region

Background: Hepatitis C virus (HCV) contains a (+) ssRNA genome with highly conserved structural, functional RNA domains, many of them with unknown roles for the consecution of the viral cycle. Such genomic domains are candidate therapeutic targets. This study reports the functional characterization...

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Autores: Fernández-Sanlés, Alba, Berzal-Herranz, Beatriz, González-Matamala, Rodrigo, Ríos-Marco, Pablo, Romero-López, Cristina, Berzal-Herranz, Alfredo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/121932
Acceso en línea:http://hdl.handle.net/10261/121932
Access Level:acceso abierto
Palabra clave:RNA aptamers
AntiHCV Aptamers
HCV genome
CRE
5BSL3.2
functional RNA domains
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spelling RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE RegionFernández-Sanlés, AlbaBerzal-Herranz, BeatrizGonzález-Matamala, RodrigoRíos-Marco, PabloRomero-López, CristinaBerzal-Herranz, AlfredoRNA aptamersAntiHCV AptamersHCV genomeCRE5BSL3.2functional RNA domainsBackground: Hepatitis C virus (HCV) contains a (+) ssRNA genome with highly conserved structural, functional RNA domains, many of them with unknown roles for the consecution of the viral cycle. Such genomic domains are candidate therapeutic targets. This study reports the functional characterization of a set of aptamers targeting the cis-acting replication element (CRE) of the HCV genome, an essential partner for viral replication and also involved in the regulation of protein synthesis. Methods: Forty-four aptamers were tested for their ability to interfere with viral RNA synthesis in a subgenomic replicon system. Some of the most efficient inhibitors were further evaluated for their potential to affect the recruitment of the HCV RNA-dependent RNA polymerase (NS5B) and the viral translation in cell culture. Results: Four aptamers emerged as potent inhibitors of HCV replication by direct interaction with functional RNA domains of the CRE, yielding a decrease in the HCV RNA levels higher than 90%. Concomitantly, one of them also induced a significant increase in viral translation (>50%). The three remaining aptamers efficiently competed with the binding of the NS5B protein to the CRE. Conclusions: Present findings confirm the potential of the CRE as an anti-HCV target and support the use of aptamers as molecular tools for investigating the functionality of RNA domains in viral genomes.Spanish Ministry of Economy and Competitiveness, BFU2012-31213 and Junta de Andalucía, CVI-7430, to A.B.-H.; FEDER funds from the EU. We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)Peer reviewedSpringer NatureConsejo Superior de Investigaciones Científicas (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201520152015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/121932reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés10.3390/molecules200916030Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1219322026-05-22T06:33:51Z
dc.title.none.fl_str_mv RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region
title RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region
spellingShingle RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region
Fernández-Sanlés, Alba
RNA aptamers
AntiHCV Aptamers
HCV genome
CRE
5BSL3.2
functional RNA domains
title_short RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region
title_full RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region
title_fullStr RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region
title_full_unstemmed RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region
title_sort RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region
dc.creator.none.fl_str_mv Fernández-Sanlés, Alba
Berzal-Herranz, Beatriz
González-Matamala, Rodrigo
Ríos-Marco, Pablo
Romero-López, Cristina
Berzal-Herranz, Alfredo
author Fernández-Sanlés, Alba
author_facet Fernández-Sanlés, Alba
Berzal-Herranz, Beatriz
González-Matamala, Rodrigo
Ríos-Marco, Pablo
Romero-López, Cristina
Berzal-Herranz, Alfredo
author_role author
author2 Berzal-Herranz, Beatriz
González-Matamala, Rodrigo
Ríos-Marco, Pablo
Romero-López, Cristina
Berzal-Herranz, Alfredo
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv RNA aptamers
AntiHCV Aptamers
HCV genome
CRE
5BSL3.2
functional RNA domains
topic RNA aptamers
AntiHCV Aptamers
HCV genome
CRE
5BSL3.2
functional RNA domains
description Background: Hepatitis C virus (HCV) contains a (+) ssRNA genome with highly conserved structural, functional RNA domains, many of them with unknown roles for the consecution of the viral cycle. Such genomic domains are candidate therapeutic targets. This study reports the functional characterization of a set of aptamers targeting the cis-acting replication element (CRE) of the HCV genome, an essential partner for viral replication and also involved in the regulation of protein synthesis. Methods: Forty-four aptamers were tested for their ability to interfere with viral RNA synthesis in a subgenomic replicon system. Some of the most efficient inhibitors were further evaluated for their potential to affect the recruitment of the HCV RNA-dependent RNA polymerase (NS5B) and the viral translation in cell culture. Results: Four aptamers emerged as potent inhibitors of HCV replication by direct interaction with functional RNA domains of the CRE, yielding a decrease in the HCV RNA levels higher than 90%. Concomitantly, one of them also induced a significant increase in viral translation (>50%). The three remaining aptamers efficiently competed with the binding of the NS5B protein to the CRE. Conclusions: Present findings confirm the potential of the CRE as an anti-HCV target and support the use of aptamers as molecular tools for investigating the functionality of RNA domains in viral genomes.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/121932
url http://hdl.handle.net/10261/121932
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv 10.3390/molecules200916030
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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