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HIV-1-Specific CD8⁺ T Cell Responses and Viral Evolution in Women and Infants¹

Victor Sanchez-Merino^*, Siwei Nie^*, and Katherine Luzuriaga^2,*

^* Department of Pediatrics/Program in Molecular Medicine and Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, MA 01605

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 quasispecies. 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.

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