title: Population-specific evolution of HIV Gag epitopes in genetically diverged patients.
abstract: BACKGROUND
  Under the host selection pressure HIV evolves rapidly to override crucial steps in the antigen presentation pathway. This allows the virus to escape binding and recognition by cytotoxic T lymphocytes. Selection pressures on HIV can be unique depending on the immunogenetics of host populations. It is therefore logical to hypothesize that the virus evolving in a given population will carry signature mutations that will allow it to survive in that particular host milieu.
  
  
  OBJECTIVE
  The aim of this study was to perform a comparative analysis of HIV-1 Gag subtype A sequences from two genetically diverged populations, namely, Kenyan and Pakistani. We analyzed unique mutations that could intercept the antigen processing pathway and potentially change the repertoire of Gag epitopes in each study group.
  
  
  METHODS
  Twenty-nine Kenyan and 56 Pakistani samples from HIV-1 subtype A-infected patients were used in this study. The HIV-1 gag region p24 and p2p7p1p6 was sequenced and mutations affecting proteasomal degradation, TAP binding, HLA binding and CTL epitope generation, were analyzed using the in silico softwares NetChop and MAPPP, TAPPred, nHLAPred and CTLPred, respectively.
  
  
  RESULTS
  Certain mutations unique to either Pakistani or Kenyan patients were observed to affect sites for proteasomal degradation, TAP binding, and HLA binding. As a consequence of these mutations, epitope pattern in these populations was altered.
  
  
  CONCLUSIONS
  Unique selection pressures can steer the direction of viral epitope evolution in the host populations. Population-specific HIV epitopes have to be taken into account while designing treatment as well as vaccine for HIV.
authors: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors: Syed H
authors: SH
authors: Abidi
authors: Aniqa
authors: A
authors: Shahid
authors: Laila S
authors: LS
authors: Lakhani
authors: Muhammad R
authors: MR
authors: Khanani
authors: Peter
authors: P
authors: Ojwang
authors: Nancy
authors: N
authors: Okinda
authors: Reena
authors: R
authors: Shah
authors: Farhat
authors: F
authors: Abbas
authors: Sarah
authors: S
authors: Rowland-Jones
authors: Syed
authors: S
authors: Ali
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D000939:Epitopes / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics; D006680:HLA Antigens; D054884:Host-Pathogen Interactions; D006801:Humans; D007630:Kenya; D008969:Molecular Sequence Data; D009154:Mutation; D010154:Pakistan; D016415:Sequence Alignment; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*
chemical_list: D000939:Epitopes; D006680:HLA Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus