HIV-1-specific CD8+ T cell responses and viral evolution in women and infants
Department of Pediatrics; Program in Molecular Medicine; Graduate School of Biomedical Sciences, Program in Immunology and Virology
Adult; Amino Acid Sequence; Base Sequence; CD8-Positive T-Lymphocytes; DNA, Viral; *Disease Transmission, Vertical; Epitopes; Female; Gene Products, gag; Gene Products, nef; Genes, gag; Genes, nef; HIV Infections; HIV-1; Humans; Infant; Infant, Newborn; Lymphocyte Activation; Molecular Sequence Data; Mutation; Pregnancy; Selection (Genetics); Sequence Homology, Amino Acid; Variation (Genetics); nef Gene Products, Human Immunodeficiency Virus
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences | Pediatrics
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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Citation: J Immunol. 2005 Nov 15;175(10):6976-86.