Conflicting selection pressures on T-cell epitopes in HIV-1 subtype B

Abstract

Analysis of population-level polymorphism in eight coding genes of human immunodeficiency virus type 1 (HIV-1) subtype B revealed evidence not only of past purifying selection, but also of abundant slightly deleterious nonsynonymous variants subject to ongoing purifying selection. Both CD4 and CTL epitopes showed an excess of nonsynonymous variants that were singletons (occurring in just one sequence) in our dataset. Overall, median gene diversities at polymorphic nonsynonymous sites were highest at sites located in neither CD4 nor CTL epitopes, while polymorphic nonsynonymous sites in CD4 epitopes revealed the lowest median gene diversity. Our results support the hypothesis that there is an evolutionary conflict between immune escape and functional constraint on epitopes recognized by host T-cells, and suggest that amino acid sequences of CD4 epitopes are subject to particularly strong functional constraint.

Fig. 1

Median gene diversity in non-epitope (NonEp) and in CD4 epitope and CTL epitope regions of (A) polymorphic synonymous and (B) polymorphic nonsynonymous sites for all genes. Numbers of sites in each category are shown. For both synonymous and nonsynonymous polymorphic sites, median gene diversity differed significantly among categories of sites (Kruskal-Wallis test, P<0.001). Mann-Whitney tests of the hypothesis that median gene diversity in a given category for synonymous polymorphic sites equals the corresponding value for nonsynonymous polymorphic sites: *P<0.001, ** P<0.01.