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Influence of mutation and recombination on HIV-1 in vitro fitness recovery

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dc.contributor.authorArenas, Miguel
dc.contributor.authorLorenzo-Redondo, Ramon
dc.contributor.authorLopez-Galindez, Luis Cecilio
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.contributor.funderPlan Nacional de I+D+i (España)es_ES
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)es_ES
dc.contributor.funderFundação para a Ciência e Tecnologia (Portugal)es_ES
dc.date.accessioned2024-02-02T19:45:09Z
dc.date.available2024-02-02T19:45:09Z
dc.date.issued2016-01
dc.description.abstractThe understanding of the evolutionary processes underlying HIV-1 fitness recovery is fundamental for HIV-1 pathogenesis, antiretroviral treatment and vaccine design. It is known that HIV-1 can present very high mutation and recombination rates, however the specific contribution of these evolutionary forces in the "in vitro" viral fitness recovery has not been simultaneously quantified. To this aim, we analyzed substitution, recombination and molecular adaptation rates in a variety of HIV-1 biological clones derived from a viral isolate after severe population bottlenecks and a number of large population cell culture passages. These clones presented an overall but uneven fitness gain, mean of 3-fold, respect to the initial passage values. We found a significant relationship between the fitness increase and the appearance and fixation of mutations. In addition, these fixed mutations presented molecular signatures of positive selection through the accumulation of non-synonymous substitutions. Interestingly, viral recombination correlated with fitness recovery in most of studied viral quasispecies. The genetic diversity generated by these evolutionary processes was positively correlated with the viral fitness. We conclude that HIV-1 fitness recovery can be derived from the genetic heterogeneity generated through both mutation and recombination, and under diversifying molecular adaptation. The findings also suggest nonrandom evolutionary pathways for in vitro fitness recovery.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipWe want to thank Daniel Wilson for helpful comments. We also want to thanks two anonymous reviewers for their insightful comments. Work in CNM is supported by grants SAF SAF 2010-17226 from MICIN Spain and grant FIS (PI13/02269) from the Fondo de Investigaciones Sanitarias (ISCIII) and in part by the RETIC de Investigación en SIDA (Red de grupos 173) of the Fondo de Investigaciones Sanitarias (FIS). This work has been partially funded by the RD12/0017/0036 Project as part of the Plan Nacional R+D+I and cofinanced by ISCIII, Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER). MA was supported by the Spanish Government through the “Juan de la Cierva” fellowship JCI-2011-10452 and by the Portuguese Government through the FCT Starting Grant IF/00955/2014.es_ES
dc.format.numberPt Aes_ES
dc.format.page264-270es_ES
dc.format.volume94es_ES
dc.identifier.citationMol Phylogenet Evol. 2016 Jan;94(Pt A):264-70.es_ES
dc.identifier.doi10.1016/j.ympev.2015.09.001es_ES
dc.identifier.e-issn1095-9513es_ES
dc.identifier.journalMolecular phylogenetics and evolutiones_ES
dc.identifier.pubmedID26358613es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/17443
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/MICINN//SAF2010-17226/ES/CARACTERIZACION DE VARIANTES NO PATOGENICOS DEL VIH OBTENIDOS "EX VIVO" E "IN VITRO" PARA EL ESTUDIO DE LA PATOGENIA DE LA INFECCION/es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/RD12/0017/0036es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/MICINN//JCI-2011-10452/ES/JCI-2011-10452/es_ES
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/null/null/Subprograma de proyectos de investigacion en salud (AES 2013) (2013)/PI13/02269es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.ympev.2015.09.001es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHIV-1 molecular evolutiones_ES
dc.subjectMutationes_ES
dc.subjectViral recombinationes_ES
dc.subjectMolecular 40 adaptationes_ES
dc.subjectGenetic heterogeneityes_ES
dc.subjectFitness recoveryes_ES
dc.subject.meshGenetic Fitnesses_ES
dc.subject.meshAdaptation, Biologicales_ES
dc.subject.meshEvolution, Moleculares_ES
dc.subject.meshHIV Infectionses_ES
dc.subject.meshHIV-1es_ES
dc.subject.meshHumanses_ES
dc.subject.meshMutationes_ES
dc.subject.meshPhylogenyes_ES
dc.subject.meshRecombination, Genetices_ES
dc.titleInfluence of mutation and recombination on HIV-1 in vitro fitness recoveryes_ES
dc.typeresearch articlees_ES
dc.type.hasVersionAMes_ES
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscoveryfd4281bc-05f4-4860-a6fc-5e78a1a1f856
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