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

• Published in: The Journal of immunology (1950) 2005-11, Vol.175 (10), p.6976-6986
• Main Authors: Sanchez-Merino, Victor, Nie, Siwei, Luzuriaga, Katherine
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Base Sequence; CD8-Positive T-Lymphocytes - immunology; DNA, Viral - genetics; Epitopes - genetics; Female; Gene Products, gag - genetics; Gene Products, nef - genetics; Genes, gag; Genes, nef; Genetic Variation; HIV Infections - immunology; HIV Infections - transmission; HIV Infections - virology; HIV-1 - genetics; HIV-1 - immunology; Humans; In Vitro Techniques; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Lymphocyte Activation; Molecular Sequence Data; Mutation; nef Gene Products, Human Immunodeficiency Virus; Pregnancy; Selection, Genetic; Sequence Homology, Amino Acid
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.175.10.6976

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.