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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. OBJECTIVES: 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. CONCLUSION: 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.

Original publication

DOI

10.1016/j.meegid.2013.02.003

Type

Journal article

Journal

Infect Genet Evol

Publication Date

06/2013

Volume

16

Pages

78 - 86

Keywords

Amino Acid Sequence, Base Sequence, Epitopes, Evolution, Molecular, HIV Infections, HIV-1, HLA Antigens, Host-Pathogen Interactions, Humans, Kenya, Molecular Sequence Data, Mutation, Pakistan, Sequence Alignment, gag Gene Products, Human Immunodeficiency Virus