Letters to Nature
Nature 412, 334-338 (19 July 2001) | doi:10.1038/35085576; Received 13 February 2001; Accepted 15 May 2001
Evolution and transmission of stable CTL escape mutations in HIV infection
Philip J. R. Goulder1,2, Christian Brander1, Yanhua Tang1, Cecile Tremblay1, Robert A. Colbert3, Marylyn M. Addo1, Eric S. Rosenberg1, Thi Nguyen1, Rachel Allen4, Alicja Trocha1, Marcus Altfeld1, Suqin He1, Michael Bunce5, Robert Funkhouser6, Stephen I. Pelton7, Sandra K. Burchett2, Kenneth McIntosh2, Bette T. M. Korber6 and Bruce D. Walker1
- Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02114, USA
- Division of Infectious Diseases, The Children's Hospital, and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA
- William S. Rowe Division of Rheumatology, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039, USA
- Department of Pathology, Cambridge University, Cambridge CB2 1QP, UK
- Oxford Transplant Centre, Churchill Hospital, Oxford OX3 7LJ, UK
- Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
- Section of Pediatric Infectious Diseases, Boston Medical Center, Boston, Massachusetts 02118, USA
Correspondence to: Philip J. R. Goulder1,2 Correspondence and requests for materials should be addressed to P.J.R.G. (e-mail: Email: goulder@helix.mgh.harvard.edu).
Increasing evidence indicates that potent anti-HIV-1 activity is mediated by cytotoxic T lymphocytes (CTLs)1, 2, 3; 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 infection4. In adults, mutations in a dominant and highly conserved B27-restricted Gag CTL epitope lead to loss of recognition and disease progression4, 5, 6. 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.