Sequence variation occurs in CD4 Epitopes during early HIV infection

Objective: To determine whether viral sequence variation occurs in HIV-specific CD4 epitopes during early HIV infection. Methods: Gag, Net, and integrase (Int) sequences were obtained from the plasma of 7 subjects identified during acute HIV-1 infection. Changes in the viral sequence were determined based on comparison of sequences obtained at 2 time points during early infection. Peptide-specific CD4(+) T-cell responses were measured at matched time points using interferon-gamma enzyme-linked immunosorbent spot assays to identify CD4 epitopes. Results: An average of 4 mutations were identified per subject. The majority of the mutations were nonsynonymous and resulted in a total of 6 amino acid changes in Gag, 7 changes in Nef, and 6 changes and a deletion in Int. Half of the sequence changes were within recognized CD4 epitopes. Mutations within CD4 epitopes were coincident with changes in the peptide-specific CD4 response. Conclusion: These data indicate that sequence variation occurs within recognized CD4 epitopes during early HIV infection. Furthermore, it suggests that mutations within HIV-specific CD4 epitopes may affect T helper cell function.