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 pa tients enrolled in a phase I trial of recombinant gp160. Methods: Sero logic responses to the HIVLAI V3 loop and autologous V3 loop DNA seque nces were sequentially determined over a 3-4-year interval. Results: S ix patients either seroconverted or had a greater than or equal to 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 less than or equal to 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 immunos orbent assay technique did not show a distinct binding preference for autologous versus heterologous V3 loop peptides. Thus, we interpret se roreactivity to the heterologous HIVLAI V3 loop to reflect the broadne ss of the V3 immune response rather than a direct measure of epitope-s pecific Immune pressure. Conclusions: These data suggest that the broa dness of serologic responses to viral epitopes are reflected in the ra te 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.