Evolution and transmission of stable CTL escape mutations in HIV infection.

Journal article

Increasing evidence indicates that potent anti-HIV-1 activity is mediated by cytotoxic T lymphocytes (CTLs); however, the effects of this immune pressure on viral transmission and evolution have not been determined. Here we investigate mother-child transmission in the setting of human leukocyte antigen (HLA)-B27 expression, selected for analysis because it is associated with prolonged immune containment in adult infection. In adults, mutations in a dominant and highly conserved B27-restricted Gag CTL epitope lead to loss of recognition and disease progression. In mothers expressing HLA-B27 who transmit HIV-1 perinatally, we document transmission of viruses encoding CTL escape variants in this dominant Gag epitope that no longer bind to B27. Their infected infants target an otherwise subdominant B27-restricted epitope and fail to contain HIV replication. These CTL escape variants remain stable without reversion in the absence of the evolutionary pressure that originally selected the mutation. These data suggest that CTL escape mutations in epitopes associated with suppression of viraemia will accumulate as the epidemic progresses, and therefore have important implications for vaccine design.

Authors: Goulder, P; Brander, C; Tang, Y; Tremblay, C; Colbert, R

• Publication status: Published
• Journal: Nature
• Volume: 412
• Issue: 6844
• Pages: 334-338
• Publication date: 2001-07-01
• DOI: 10.1038/35085576
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English
• Keywords: Epitopes, T-Lymphocyte; DNA, Viral; T-Lymphocytes, Cytotoxic; HLA-B27 Antigen; Histocompatibility Testing; Disease Progression; Mutation; Infectious Disease Transmission, Vertical; Humans; Female; Adult; HIV-1; Child; HIV Infections