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 epi...

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Bibliographic Details
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
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.175.10.6976