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dc.contributor.authorBorderia, Antonio V. 
dc.contributor.authorLorenzo-Redondo, Ramon 
dc.contributor.authorPernas, Maria 
dc.contributor.authorCasado, Concepcion 
dc.contributor.authorAlvaro-Cifuentes, Tamara 
dc.contributor.authorDomingo, Esteban
dc.contributor.authorLopez-Galindez, Luis Cecilio
dc.identifier.citationPLoS One. 2010 Apr 26;5(4):e10319.es_ES
dc.description.abstractBACKGROUND: Fitness recovery of HIV-1 "in vitro" was studied using viral clones that had their fitness decreased as a result of plaque-to-plaque passages. PRINCIPAL FINDINGS: After ten large population passages, the viral populations showed an average increase of fitness, although with wide variations among clones. While 5 clones showed significant fitness increases, 3 clones showed increases that were only marginally significant (p<0.1), and 4 clones did not show any change. Fitness recovery was not accompanied by an increase in p24 production, but was associated with an increase in viral titer. Few mutations (an average of 2 mutations per genome) were detected in the consensus nucleotide sequence of the entire genome in all viral populations. Five of the populations did not fix any mutation, and three of them displayed marginally significant fitness increases, illustrating that fitness recovery can occur without detectable alterations of the consensus genomic sequence. The investigation of other possible viral factors associated with the initial steps of fitness recovery, showed that viral quasispecies heterogeneity increased between the initial clones and the passaged populations. A direct statistical correlation between viral heterogeneity and viral fitness was obtained. CONCLUSIONS: Thus, the initial fitness recovery of debilitated HIV-1 clones was mediated by an increase in quasispecies heterogeneity. This observation, together with the invariance of the consensus sequence despite fitness increases demonstrates the relevance of quasispecies heterogeneity in the evolution of HIV-1 in cell culture.es_ES
dc.description.sponsorshipWork in the Centro Nacional de Microbiología was supported by grants, SAF 2005/03833, SAF 2007/61036 by the Plan Nacional del SIDA and in part by the Red Temática Cooperativa de investigación en SIDA (Red de grupos 173) of the Fondo de Investigaciones Sanitarias de la Seguridad Social (FISss) and Fundación para la Investigación y la Prevención del SIDA en España (FIPSE) grant 36558/06, 36641/07, 36779/08, 36641/07 and 360766/09. Work in the Centro de Biología Molecular “Severo Ochoa” was supported by grant BFU 2008-02816/BMC from Ministerio de Ciencia e Innovación, FIPSE 36558/06 and 360766/09 and Fundación Ramón Areces. Centro de Investigaciones Biomédica en Red (CIBER): enfermedades hepáticas y digestivas (ehd) is funded by Instituto de Salud Carlos III. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.publisherPublic Library of Science (PLOS) es_ES
dc.subject.meshConsensus Sequence es_ES
dc.subject.meshGenome, Viral es_ES
dc.subject.meshHIV-1 es_ES
dc.subject.meshMutation es_ES
dc.subject.meshSelection, Genetices_ES
dc.subject.meshSerial Passage es_ES
dc.subject.meshVirology es_ES
dc.subject.meshGenetic Fitness es_ES
dc.subject.meshGenetic Heterogeneity es_ES
dc.titleInitial fitness recovery of HIV-1 is associated with quasispecies heterogeneity and can occur without modifications in the consensus sequencees_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderFundación para la Investigación y la Prevención del Sida en España 
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.contributor.funderFundación Ramón Areces 
dc.contributor.funderInstituto de Salud Carlos III 
dc.identifier.journalPloS onees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU 2008-02816/BMCes_ES
dc.rights.accessRightsopen accesses_ES

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Atribución 4.0 Internacional
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