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An integrated map of HIV genome-wide variation from a population perspective

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dc.creatorLi, Guangdispa
dc.creatorPiampongsant, Supinyaspa
dc.creatorFaria, Nuno Rodriguesspa
dc.creatorVoet, Arnoutspa
dc.creatorPineda-Peña, Andrea-Clemenciaspa
dc.creatorKhouri, Ricardospa
dc.creatorLemey, Philippespa
dc.creatorVandamme, Anne-Miekespa
dc.creatorTheys, Kristofspa
dc.date.accessioned2020-05-25T23:58:53Z
dc.date.available2020-05-25T23:58:53Z
dc.date.created2015spa
dc.description.abstractBackground: The HIV pandemic is characterized by extensive genetic variability, which has challenged the development of HIV drugs and vaccines. Although HIV genomes have been classified into different types, groups, subtypes and recombinants, a comprehensive study that maps HIV genome-wide diversity at the population level is still lacking to date. This study aims to characterize HIV genomic diversity in large-scale sequence populations, and to identify driving factors that shape HIV genome diversity. Results: A total of 2996 full-length genomic sequences from 1705 patients infected with 16 major HIV groups, subtypes and circulating recombinant forms (CRFs) were analyzed along with structural, immunological and peptide inhibitor information. Average nucleotide diversity of HIV genomes was almost 50% between HIV-1 and HIV-2 types, 37.5% between HIV-1 groups, 14.7% between HIV-1 subtypes, 8.2% within individual HIV-1 subtypes and less than 1% within single patients. Along the HIV genome, diversity patterns and compositions of nucleotides and amino acids were highly similar across different groups, subtypes and CRFs. Current HIV-derived peptide inhibitors were predominantly derived from conserved, solvent accessible and intrinsically ordered structures in the HIV-1 subtype B genome. We identified these conserved regions in Capsid, Nucleocapsid, Protease, Integrase, Reverse transcriptase, Vpr and the GP41 N terminus as potential drug targets. In the analysis of factors that impact HIV-1 genomic diversity, we focused on protein multimerization, immunological constraints and HIV-human protein interactions. We found that amino acid diversity in monomeric proteins was higher than in multimeric proteins, and diversified positions were preferably located within human CD4 T cell and antibody epitopes. Moreover, intrinsic disorder regions in HIV-1 proteins coincided with high levels of amino acid diversity, facilitating a large number of interactions between HIV-1 and human proteins. Conclusions: This first large-scale analysis provided a detailed mapping of HIV genomic diversity and highlighted drug-target regions conserved across different groups, subtypes and CRFs. Our findings suggest that, in addition to the impact of protein multimerization and immune selective pressure on HIV-1 diversity, HIV-human protein interactions are facilitated by high variability within intrinsically disordered structures. © 2015 Li et al.; licensee BioMed Central.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1186/s12977-015-0148-6
dc.identifier.issn17424690
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/22943
dc.language.isoengspa
dc.publisherBioMed Central Ltd.spa
dc.relation.citationIssueNo. 1
dc.relation.citationTitleRetrovirology
dc.relation.citationVolumeVol. 12
dc.relation.ispartofRetrovirology, ISSN:17424690, Vol.12, No.1 (2015)spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84928747332&doi=10.1186%2fs12977-015-0148-6&partnerID=40&md5=bc1a745def09d82e0d432d7a50f024f3spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordEpitopespa
dc.subject.keyworddnaeng
dc.subject.keywordIntegrasespa
dc.subject.keywordNucleocapsid proteinspa
dc.subject.keywordProteinasespa
dc.subject.keywordRna directed dna polymerasespa
dc.subject.keywordVpr proteinspa
dc.subject.keywordArticlespa
dc.subject.keywordCd4 lymphocyte countspa
dc.subject.keywordCladisticsspa
dc.subject.keywordGene mappingspa
dc.subject.keywordGenetic analysisspa
dc.subject.keywordGenetic associationspa
dc.subject.keywordGenetic conservationspa
dc.subject.keywordGenetic variabilityspa
dc.subject.keywordHuman immunodeficiency virusspa
dc.subject.keywordHuman immunodeficiency virus 1spa
dc.subject.keywordHuman immunodeficiency virus 2spa
dc.subject.keywordNonhumanspa
dc.subject.keywordOpen reading framespa
dc.subject.keywordPhylogenyspa
dc.subject.keywordPromoter regionspa
dc.subject.keywordProtein multimerizationspa
dc.subject.keywordSequence analysisspa
dc.subject.keywordViral geneticsspa
dc.subject.keywordVirus particlespa
dc.subject.keywordDna sequencespa
dc.subject.keywordGenetic variabilityspa
dc.subject.keywordGeneticsspa
dc.subject.keywordHumanspa
dc.subject.keywordHuman immunodeficiency virus infectionspa
dc.subject.keywordVirologyspa
dc.subject.keywordVirus genomespa
dc.subject.keywordHuman immunodeficiency virus 1spa
dc.subject.keywordHuman immunodeficiency virus 2spa
dc.subject.keywordMiridaespa
dc.subject.keywordGenetic variationspa
dc.subject.keywordGenomeeng
dc.subject.keywordHiv infectionsspa
dc.subject.keywordHiv-1spa
dc.subject.keywordHumansspa
dc.subject.keywordSequence analysiseng
dc.subject.keywordConservationspa
dc.subject.keywordGenomic diversityspa
dc.subject.keywordHiv genomespa
dc.subject.keywordHiv inter- and inter-clade genetic diversityspa
dc.subject.keywordHiv phylogenetic treespa
dc.subject.keywordHiv-human protein interactionspa
dc.subject.keywordPeptide inhibitorspa
dc.subject.keywordProtein intrinsic disorderspa
dc.subject.keywordProtein multimerizationspa
dc.subject.keywordSelective pressurespa
dc.titleAn integrated map of HIV genome-wide variation from a population perspectivespa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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