An introduction to a novel population genetic approach for HIV characterization.

The rapid evolution of the HIV genome is influenced in part by host selection pressure, which may cause parallel evolution among strains under shared selection pressures. To understand the mechanisms behind HIV-host immune escape across host populations, researchers have compared signatures of positive selection pressure on HIV codons across HIV subtypes and across phylogenetic groups of isolates within major subtypes, all relying on a criterion of phylogenetic separation. The HIV codon sites that retain diversity, evolve convergently among sets of hosts (cohorts) and diverge between cohorts may be phylogenetically undiagnostic (reveal little information about the relationship of the strains) and thus undetectable on a tree. We propose a new approach to characterizing genetic divergence among isolates using existing population genetic methods to better understand HIV response to host selection pressures. The approach combines population genetic statistical methods with codon analysis to identify putative amino acid sites evolving convergently. To illustrate the approach, we compared the C2-V3-C3 region of the envelope protein of HIV-1 clade B isolates between Haiti and USA hosts. This region showed no phylogenetic separation between host populations. Still, we identified codon sites in the C2-V3-C3 HIV-1 region that may have evolved differently between the two host populations. The sites are localized in human leukocyte antigen (HLA) class I binding epitopes, N-glycosylation motifs or both and are limited to the C2 and C3 regions. Our method provides a potential means to reveal candidate sites actively involved in HIV-1 immune escape that would otherwise be missed if a requisite for phylogenetic distinctiveness was made a priori. This strategy may prove to be a helpful way to characterize HIV genetic variation among hosts with suspected selection pressure differences, like progressors versus non-progressors.