Title

Population-specific evolution of HIV Gag epitopes in genetically diverged patients.

Document Type

Article

Department

Urology

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.

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 silicosoftwares 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.

Publication

Infection, Genetics and Evolution