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

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...

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Autores:
Tipo de recurso:
Fecha de publicación:
2015
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/22943
Acceso en línea:
https://doi.org/10.1186/s12977-015-0148-6
https://repository.urosario.edu.co/handle/10336/22943
Palabra clave:
Epitope
Human immunodeficiency virus vaccine
Integrase
Nucleocapsid protein
Proteinase
Rna directed dna polymerase
Vpr protein
Article
Cd4 lymphocyte count
Cladistics
Gene mapping
Genetic analysis
Genetic association
Genetic conservation
Genetic variability
Human immunodeficiency virus
Human immunodeficiency virus 1
Human immunodeficiency virus 2
Nonhuman
Open reading frame
Phylogeny
Promoter region
Protein multimerization
Sequence analysis
Viral genetics
Virus particle
Dna sequence
Genetic variability
Genetics
Human
Human immunodeficiency virus infection
Virology
Virus genome
Human immunodeficiency virus 1
Human immunodeficiency virus 2
Miridae
Genetic variation
Hiv infections
Hiv-1
Humans
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
dna
viral
Genome
Sequence analysis
Rights
License
Abierto (Texto Completo)
Description
Summary: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. © 2015 Li et al.; licensee BioMed Central.