V3 seroreactivity and sequence variation: Tracking the emergence of V3 genotypic variation in HIV-1-infected patients

Objective: To investigate the relationship between V3-specific immune responses and viral quasispecies evolution in 10 HIV-1-seropositive patients enrolled in a phase I trial of recombinant gp160. Methods: Serologic responses to the HIV(LAI) V3 loop and autologous V3 loop DNA sequences were sequentially determined over a 3-4-year interval. Results: Six patients either seroconverted or had a ≥ 42-fold boost in titer to the V3 reagent associated with an average of 3.2 amino-acid changes in their autologous V3 loops. Four patients with ≤ 11-fold change in titer to the V3 loop showed an average of 0.75 amino-acid changes. Attempts to measure autologous V3 loop responses in four patients using a peptide enzyme-linked immunosorbent assay technique did not show a distinct binding preference for autologous versus heterologous V3 loop peptides. Thus, we interpret seroreactivity to the heterologous HIV(LAI) V3 loop to reflect the broadness of the V3 immune response rather than a direct measure of epitope-specific Immune pressure. Conclusions: These data suggest that the broadness of serologic responses to viral epitopes are reflected in the rate of evolution of their cognate coding sequences and support the view that the immune response to HIV-1 results in the continuous selection of new viral variants during the course of disease.