Abstract
ObjectiveThe aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes.MethodsWe used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G→A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined.ResultsThe most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956±1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2–3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005–2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005–2010.ConclusionIt appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences.
Highlights
Under selection pressures from host immunity, human immunodeficiency virus type 1 (HIV-1) rapidly mutates, which allows the amplification of escape mutations that enables the virus to evade the host’s immune response [1,2,3]
In the current study, taking into account the sequences from years 1985 to 2010, we have analysed the divergence and evolution of HIV gag. We focus on both time-dependent as well as cohort-specific evolution of the HIV-1 subtype A gag gene, and present an analysis of evolutionary dynamics of HIV-1 subtype A on a global level, especially with respect to the evolution of gag epitopes
Phylogenetic relationships among the HIV subtype A gag sequences were inferred through a Maximum Likelihood (ML) tree
Summary
Under selection pressures from host immunity, human immunodeficiency virus type 1 (HIV-1) rapidly mutates, which allows the amplification of escape mutations that enables the virus to evade the host’s immune response [1,2,3]. Sequences of HIV-1 subtype A that were first deposited in the Los Alamos National Laboratory (LANL) HIV Sequence Database were of African origin, from mid-80s. Analysis of the evolutionary patterns of a virus in the context of its host populations sheds light on the selection pressures on viruses that are associated with specific host immune milieus [6,7]. This type of information is useful in designing vaccines and drugs against the virus
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