| Author | Li, Guangdi | |
| Author | Piampongsant, Supinya | |
| Author | Faria, Nuno Rodrigues | |
| Author | Voet, Arnout | |
| Author | Peña, Andrea-Clemencia Pineda | |
| Author | Cunha, Antonio Ricardo Khouri | |
| Author | Lemey, Philippe | |
| Author | Vandamme, Anne-Mieke | |
| Author | Theys, Kristof | |
| Access date | 2015-05-28T16:52:46Z | |
| Available date | 2015-05-28T16:52:46Z | |
| Document date | 2015 | |
| Citation | LI, G. et al. An integrated map of HIV genome-wide variation from a population perspective. Retrovirology, v. 12, n. 1, p. 18, 2015. | pt_BR |
| ISSN | 1742-4690 | |
| URI | https://www.arca.fiocruz.br/handle/icict/10577 | |
| Language | eng | pt_BR |
| Publisher | BioMed Central | pt_BR |
| Rights | open access | pt_BR |
| Title | An integrated map of HIV genome-wide variation from a population perspective. | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1186/s12977-015-0148-6 | |
| Abstract | BACKGROUND: 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. | pt_BR |
| Affilliation | Central South University. Metabolic Syndrome Research Center. Second Xiangya Hospital. Changsha, Hunan, China / Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium | pt_BR |
| Affilliation | Central South University. Metabolic Syndrome Research Center. Second Xiangya Hospital. Changsha, Hunan, China / Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium | pt_BR |
| Affilliation | University of Oxford. Department of Zoology. Oxford, UK | pt_BR |
| Affilliation | RIKEN Institute Laboratories. Zhang IRU. Hirosawa, Wako-shi, Saitama, Japan | pt_BR |
| Affilliation | Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium / Universidad del Rosario. Faculty of Sciences and Mathematics. Clinical and Molecular Infectious Disease Group. Bogotá, Colombia | pt_BR |
| Affilliation | Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium | pt_BR |
| Affilliation | Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium / Universidade Nova de Lisboa. Instituto de Higiene e Medicina Tropical. Centro de Malária e Outras Doenças Tropicais and Unidade de Microbiologia. Lisbon, Portugal | pt_BR |
| Affilliation | Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium | pt_BR |
| Subject | HIV genome | pt_BR |
| Subject | Genomic diversity | pt_BR |
| Subject | Conservation | pt_BR |
| Subject | Peptide inhibitor | pt_BR |
| Subject | HIV-human protein interaction | pt_BR |
| Subject | HIV | pt_BR |
| Subject | Phylogenetic tree | pt_BR |
| Subject | HIV inter- and inter-clade genetic diversity | pt_BR |
| Subject | Selective pressure | pt_BR |
| Subject | Protein multimerization | pt_BR |
| Subject | Protein intrinsic disorder | pt_BR |
| xmlui.metadata.dc.subject.ods | 10 Redução das desigualdades | |
