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dc.contributor.authorHiguera, Ignacio de laes_ES
dc.contributor.authorFerrer-Orta, Cristinaes_ES
dc.contributor.authorÁvila, Ana Isabel dees_ES
dc.contributor.authorPerales, Celiaes_ES
dc.contributor.authorSierra, Macarenaes_ES
dc.contributor.authorSingh, Kamalendraes_ES
dc.contributor.authorSarafianos, Stefan G.es_ES
dc.contributor.authorDehouck, Yveses_ES
dc.contributor.authorBastolla, Ugoes_ES
dc.contributor.authorVerdaguer, Núriaes_ES
dc.contributor.authorDomingo, Estebanes_ES
dc.date.accessioned2019-01-22T10:12:07Z-
dc.date.available2019-01-22T10:12:07Z-
dc.date.issued2017-05-01-
dc.identifier.citationGenome biology and evolution 9(5): 1212–1228 (2017)es_ES
dc.identifier.urihttp://hdl.handle.net/10261/174491-
dc.description.abstractThe selective pressures acting on viruses that replicate under enhanced mutation rates are largely unknown. Here, we describe resistance of foot-and-mouth disease virus to the mutagen 5-fluorouracil (FU) through a single polymerase substitution that prevents an excess of A to G and U to C transitions evoked by FU on the wild-type foot-and-mouth disease virus, while maintaining the same level of mutant spectrum complexity. The polymerase substitution inflicts upon the virus a fitness loss during replication in absence of FU but confers a fitness gain in presence of FU. The compensation of mutational bias was documented by in vitro nucleotide incorporation assays, and it was associated with structural modifications at the N-terminal region and motif B of the viral polymerase. Predictions of the effect of mutations that increase the frequency of G and C in the viral genome and encoded polymerase suggest multiple points in the virus life cycle where the mutational bias in favor of G and C may be detrimental. Application of predictive algorithms suggests adverse effects of the FU-directed mutational bias on protein stability. The results reinforce modulation of nucleotide incorporation as a lethal mutagenesis-escape mechanism (that permits eluding virus extinction despite replication in the presence of a mutagenic agent) and suggest that mutational bias can be a target of selection during virus replicationes_ES
dc.description.sponsorshipWork in Madrid was supported by grants [BFU2011-23604, SAF2014-52400-R, S2013/ABI2906 (PLATESA from Comunidad de Madrid/FEDER)] and Fundacion R. Areces and grant BFU2012-40020 to U.B. CIBERehd is funded by Instituto de Salud Carlos III. Work in Barcelona was supported by grants [BIO2011-24333, BIO2014-54588-P and MDM-2014-0435 from the Spanish MINECO]. X-ray data were collected at ALBA Synchrotron (Cerdanyola de Valles, Spain) XALOC beamline with the collaboration of ALBA staff. Financial support was provided by ALBA. C.P. is supported by the Miguel Servet program of the Instituto de Salud Carlos III (CP14/00121) cofinanced by the European Regional Development Fund (ERDF). The kinetic studies at the University of Missouri were partially supported by grant [AI076119] (National Institute of Health, USA) to S.G.S.es_ES
dc.language.isoenges_ES
dc.publisherOxford University Presses_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-52400-Res_ES
dc.relationS2013/ABI-2906/PLATESAes_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2014-54588-Pes_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/MDM-2014-0435es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rightsopenAccesses_ES
dc.subjectAntiviral resistancees_ES
dc.subjectFitnesses_ES
dc.subjectLethal mutagenesises_ES
dc.subjectFoot-and-mouth disease viruses_ES
dc.subject5-fluorouraciles_ES
dc.subjectProtein folding stabilityes_ES
dc.titleMolecular and functional bases of selection against a mutation bias in an RNA viruses_ES
dc.typeartículoes_ES
dc.identifier.doi10.1093/gbe/evx075-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1093/gbe/evx075es_ES
dc.identifier.e-issn1759-6653-
dc.rights.licensehttps://creativecommons.org/licenses/by/4.0/es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderEuropean Commissiones_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderFundación Ramón Areceses_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.contributor.funderALBA Synchrotrones_ES
dc.contributor.funderNational Institutes of Health (US)es_ES
dc.relation.csices_ES
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dc.identifier.funderhttp://dx.doi.org/10.13039/100008054es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100000002es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100012818es_ES
dc.identifier.pmid28460010-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.grantfulltextopen-
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item.cerifentitytypePublications-
item.languageiso639-1en-
item.openairetypeartículo-
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