Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints
Open Access
- 1 November 2011
- journal article
- Published by Springer Science and Business Media LLC in Retrovirology
- Vol. 8 (1), 87
- https://doi.org/10.1186/1742-4690-8-87
Abstract
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.Keywords
This publication has 26 references indexed in Scilit:
- HIV-1 adaptation to NK-cell-mediated immune pressureNature, 2011
- Extensive HLA-driven viral diversity following a narrow-source HIV-1 outbreak in rural ChinaBlood, 2011
- Coordinate linkage of HIV evolution reveals regions of immunological vulnerabilityProceedings of the National Academy of Sciences of the United States of America, 2011
- Follicular Helper CD4 T Cells (TFH)Annual Review of Immunology, 2011
- Constraints on HIV-1 Diversity from Protein StructureJournal of Virology, 2010
- Sequence Evolution of HIV-1 following Mother-to-Child TransmissionJournal of Virology, 2010
- Computational Analysis of HIV-1 Protease Protein Binding PocketsJournal of Chemical Information and Modeling, 2010
- TRIM5 Suppresses Cross-Species Transmission of a Primate Immunodeficiency Virus and Selects for Emergence of Resistant Variants in the New SpeciesPLoS Biology, 2010
- Properties of overlapping genes are conserved across microbial genomesGenome Research, 2004
- Retrovirus mutation rates and their role in genetic variation.Journal of General Virology, 1998