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 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.
Sanchez-Merino
Victor
V
Department of Pediatrics/Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Nie
Siwei
S
Luzuriaga
Katherine
K
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D005260:Female; D015683:Gene Products, gag / Q000235:genetics; D015693:Gene Products, nef / Q000235:genetics; D015750:Genes, gag; D015754:Genes, nef; D014644:Genetic Variation; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009154:Mutation; D011247:Pregnancy; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid; D054311:nef Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D000939:Epitopes; D015683:Gene Products, gag; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus