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Volume 6 Supplement 3

AIDS Vaccine 2009

P20-10. Differences in patterns of Gag-induced immunogenetic pressure occur between clades A and D chronic HIV-1 infection in a Ugandan population

Background

We previously reported slow HIV-1 disease progression in this population to be associated with the inherent host HLA B allele-mediated ability to induce broader Gag T-cell responses and faster disease progression to be more associated with clade D than A. Since Gag escape mutations often reduce viral fitness leading to significant reduction in virus replication, in this study, we evaluated the immunogenetic characteristics of clades A and D-associated escape mutations that could be harnessed for vaccine design.

Methods

The HIV-1 gag gene was sequenced to determine genetic variability in 55 HIV-1 chronically infected, ART-naive adults previously screened for Gag T-cell responses. The proportion of individuals in which Gag-induced immune escape occurred was determined in 46 individuals that had sequence data. The proportion of B57/5801-driven substitutions: A→P in p17 AISPRTLNAW and T242N in p24 TSTLQEQIAW (TW10) both known to confer protection in early infection; and substitution A163G in p24 KAFSPEVIPMF (KF11) known to confer protection in chronic infection was correlated with the infecting gag clade.

Results

Clades A1, D, and inter-subtype recombinants A1/C, A1/D occurred at frequencies 43%, 52%, 2.2% and 2.2%, (n = 46), respectively. Substitution A→P occurred in 3/41 (1 vs.2), A1 and D respectively; T242N occurred in 5/41 (1 vs. 1 vs. 3), A1, A1/C and D, respectively. Immununogenetic substitution A163G in the Gag KF11 epitope, known to confer protection in chronic HIV-1 infection, was absent in the two recombinants, but occurred in 11/44 (11/20 clade A vs. 0/24 clade D); p = 0.00012, Fisher's Exact.

Conclusion

These data suggest preferential, clade A-associated, immunogenetic selection of a dominant Gag escape mutation known to have an impact on virus replication in chronic HIV-1 disease; this may partly account for the differential disease progression we have observed in clade A and D infection, this is also relevant to HIV vaccine development.

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Correspondence to J Serwanga.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Serwanga, J., Ndembi, N., Nanteza, B. et al. P20-10. Differences in patterns of Gag-induced immunogenetic pressure occur between clades A and D chronic HIV-1 infection in a Ugandan population. Retrovirology 6, P380 (2009). https://doi.org/10.1186/1742-4690-6-S3-P380

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Keywords

  • Viral Fitness
  • Substitution A163G
  • Fast Disease Progression
  • Ugandan Population
  • Immunogenetic Characteristic