HIV-1-specific CD8+ T cell responses and viral evolution in women and infants

CD8(+) T lymphocyte responses play an important role in controlling HIV-1 replication but escape from CD8(+) T cell surveillance may limit the effectiveness of these responses. Mother-to-child transmission of CD8(+) T cell escape variants may particularly affect CD8(+) T cell recognition of infant HIV-1 epitopes. In this study, amino acid sequence variation in HIV-1 gag and nef was examined in five untreated mother-infant pairs to evaluate the potential role of CD8(+) T cell responses in the evolution of the viral quasi-species. Several CD8(+) T cell escape variants were detected in maternal plasma. Evaluation of infant plasma viruses at 1-3 mo documented heterogeneity of gag and nef gene sequences and mother-to-child transmission of CD8(+) T cell escape variants. Infant HLA haplotype and viral fitness appeared to determine the stability of the escape mutants in the infant over time. Changes in CD8(+) T cell epitope sequences were detected in infants' sequential plasma specimens, suggesting that infants are capable of generating virus-specific CD8(+) T cell responses that exert selective pressures in vivo. Altogether, these studies document that HIV-1-specific CD8(+) T cell responses contribute to the evolution of the viral quasispecies in HIV-1-infected women and their infants and may have important implications for vaccine design.