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

Detalhes bibliográficos
Autor(a) principal: Li, Guangdi
Data de Publicação: 2015
Outros Autores: Piampongsant, Supinya, Faria, Rodrigues N., Voet, Arnout, Pineda-Peña, Andrea Clemencia, Khouri, Ricardo, Lemey, Philippe, Vandamme, Anne Mieke, Theys, Kristof
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://doi.org/10.1186/s12977-015-0148-6
Resumo: PMID: 25808207 WOS:000350853000001
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spelling An integrated map of HIV genome-wide variation from a population perspectiveConservationGenomic diversityHIV genomeHIV inter- and inter-clade genetic diversityHIV phylogenetic treeHIV-human protein interactionPeptide inhibitorProtein intrinsic disorderProtein multimerizationSelective pressureVirologyInfectious DiseasesSDG 3 - Good Health and Well-beingPMID: 25808207 WOS:000350853000001Background: 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.Instituto de Higiene e Medicina Tropical (IHMT)TB, HIV and opportunistic diseases and pathogens (THOP)Global Health and Tropical Medicine (GHTM)RUNLi, GuangdiPiampongsant, SupinyaFaria, Rodrigues N.Voet, ArnoutPineda-Peña, Andrea ClemenciaKhouri, RicardoLemey, PhilippeVandamme, Anne MiekeTheys, Kristof2018-05-14T22:01:54Z2015-02-152015-02-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.1186/s12977-015-0148-6eng1742-4690PURE: 1726983http://www.scopus.com/inward/record.url?scp=84928747332&partnerID=8YFLogxKhttps://doi.org/10.1186/s12977-015-0148-6info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:20:29Zoai:run.unl.pt:10362/36934Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:30:42.588043Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv An integrated map of HIV genome-wide variation from a population perspective
title An integrated map of HIV genome-wide variation from a population perspective
spellingShingle An integrated map of HIV genome-wide variation from a population perspective
Li, Guangdi
Conservation
Genomic diversity
HIV genome
HIV inter- and inter-clade genetic diversity
HIV phylogenetic tree
HIV-human protein interaction
Peptide inhibitor
Protein intrinsic disorder
Protein multimerization
Selective pressure
Virology
Infectious Diseases
SDG 3 - Good Health and Well-being
title_short An integrated map of HIV genome-wide variation from a population perspective
title_full An integrated map of HIV genome-wide variation from a population perspective
title_fullStr An integrated map of HIV genome-wide variation from a population perspective
title_full_unstemmed An integrated map of HIV genome-wide variation from a population perspective
title_sort An integrated map of HIV genome-wide variation from a population perspective
author Li, Guangdi
author_facet Li, Guangdi
Piampongsant, Supinya
Faria, Rodrigues N.
Voet, Arnout
Pineda-Peña, Andrea Clemencia
Khouri, Ricardo
Lemey, Philippe
Vandamme, Anne Mieke
Theys, Kristof
author_role author
author2 Piampongsant, Supinya
Faria, Rodrigues N.
Voet, Arnout
Pineda-Peña, Andrea Clemencia
Khouri, Ricardo
Lemey, Philippe
Vandamme, Anne Mieke
Theys, Kristof
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Higiene e Medicina Tropical (IHMT)
TB, HIV and opportunistic diseases and pathogens (THOP)
Global Health and Tropical Medicine (GHTM)
RUN
dc.contributor.author.fl_str_mv Li, Guangdi
Piampongsant, Supinya
Faria, Rodrigues N.
Voet, Arnout
Pineda-Peña, Andrea Clemencia
Khouri, Ricardo
Lemey, Philippe
Vandamme, Anne Mieke
Theys, Kristof
dc.subject.por.fl_str_mv Conservation
Genomic diversity
HIV genome
HIV inter- and inter-clade genetic diversity
HIV phylogenetic tree
HIV-human protein interaction
Peptide inhibitor
Protein intrinsic disorder
Protein multimerization
Selective pressure
Virology
Infectious Diseases
SDG 3 - Good Health and Well-being
topic Conservation
Genomic diversity
HIV genome
HIV inter- and inter-clade genetic diversity
HIV phylogenetic tree
HIV-human protein interaction
Peptide inhibitor
Protein intrinsic disorder
Protein multimerization
Selective pressure
Virology
Infectious Diseases
SDG 3 - Good Health and Well-being
description PMID: 25808207 WOS:000350853000001
publishDate 2015
dc.date.none.fl_str_mv 2015-02-15
2015-02-15T00:00:00Z
2018-05-14T22:01:54Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://doi.org/10.1186/s12977-015-0148-6
url https://doi.org/10.1186/s12977-015-0148-6
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1742-4690
PURE: 1726983
http://www.scopus.com/inward/record.url?scp=84928747332&partnerID=8YFLogxK
https://doi.org/10.1186/s12977-015-0148-6
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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