Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints

Background The HIV-1 genome is subject to pressures that target the virus resulting in escape and adaptation. On the other hand, there is a requirement for sequence conservation because of functional and structural constraints. Mapping the sites of selective pressure and conservation on the viral ge...

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Vydáno v:Retrovirology Ročník 8; číslo 1; s. 87
Hlavní autoři: Snoeck, Joke, Fellay, Jacques, Bartha, István, Douek, Daniel C, Telenti, Amalio
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 01.11.2011
BioMed Central Ltd
Springer Nature B.V
BMC
Témata:
Amino acids
Antibodies
Biomedical and Life Sciences
Biomedicine
Cancer Research
Chromosome Mapping
Confidence intervals
evolution
Evolution, Molecular
Genetic aspects
Genetic diversity
Genome, Viral
Genomes
HIV
HIV (Viruses)
HIV Infections - virology
HIV-1 - genetics
Humans
Immune system
Infectious Diseases
Life sciences
Molecular Sequence Data
Multivariate analysis
Physiological aspects
positive selection
Protein Structure
Reading
RNA structure
RNA, Viral - genetics
Selection, Genetic
Vaccine
Viral Proteins - genetics
Virology
Belgium
United States
Switzerland
positive selection
evolution
HIV
RNA structure
ISSN:1742-4690, 1742-4690
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Shrnutí:Background The HIV-1 genome is subject to pressures that target the virus resulting in escape and adaptation. On the other hand, there is a requirement for sequence conservation because of functional and structural constraints. Mapping the sites of selective pressure and conservation on the viral genome generates a reference for understanding the limits to viral escape, and can serve as a template for the discovery of sites of genetic conflict with known or unknown host proteins. Results To build a thorough evolutionary, functional and structural map of the HIV-1 genome, complete subtype B sequences were obtained from the Los Alamos database. We mapped sites under positive selective pressure, amino acid conservation, protein and RNA structure, overlapping coding frames, CD8 T cell, CD4 T cell and antibody epitopes, and sites enriched in AG and AA dinucleotide motives. Globally, 33% of amino acid positions were found to be variable and 12% of the genome was under positive selection. Because interrelated constraining and diversifying forces shape the viral genome, we included the variables from both classes of pressure in a multivariate model to predict conservation or positive selection: structured RNA and α-helix domains independently predicted conservation while CD4 T cell and antibody epitopes were associated with positive selection. Conclusions The global map of the viral genome contains positive selected sites that are not in canonical CD8 T cell, CD4 T cell or antibody epitopes; thus, it identifies a class of residues that may be targeted by other host selective pressures. Overall, RNA structure represents the strongest determinant of HIV-1 conservation. These data can inform the combined analysis of host and viral genetic information.
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ISSN:1742-4690
1742-4690
DOI:10.1186/1742-4690-8-87