title: HIV-1 subtype A gag variability and epitope evolution.
abstract: OBJECTIVE
  The 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  It 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.
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Syed Hani
authors.initials: SH
authors.lastname: Abidi
authors.affiliation: Vanderbilt Institute of Global health, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Kalish
authors.affiliation: Department of Surgery, Aga Khan University, Karachi, Pakistan.
authors.forename: Farhat
authors.initials: F
authors.lastname: Abbas
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Syed
authors.initials: S
authors.lastname: Ali
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015331:Cohort Studies; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology*; D019143:Evolution, Molecular; D015683:Gene Products, gag / Q000737:chemistry* / Q000276:immunology*; D014644:Genetic Variation; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000276:immunology*; D006801:Humans; D016013:Likelihood Functions; D008969:Molecular Sequence Data; D010802:Phylogeny; D013997:Time Factors
chemical_list: D000939:Epitopes; D015683:Gene Products, gag