Evolution and transmission of stable CTL escape mutations in HIV infection

Philip J. R. Goulder (), Christian Brander, Yanhua Tang, Cecile Tremblay, Robert A. Colbert, Marylyn M. Addo, Eric S. Rosenberg, Thi Nguyen, Rachel Allen, Alicja Trocha, Marcus Altfeld, Suqin He, Michael Bunce, Robert Funkhouser, Stephen I. Pelton, Sandra K. Burchett, Kenneth McIntosh, Bette T. M. Korber and Bruce D. Walker
Additional contact information
Philip J. R. Goulder: Partners AIDS Research Center, Harvard Medical School
Christian Brander: Partners AIDS Research Center, Harvard Medical School
Yanhua Tang: Partners AIDS Research Center, Harvard Medical School
Cecile Tremblay: Partners AIDS Research Center, Harvard Medical School
Robert A. Colbert: Children's Hospital Medical Center
Marylyn M. Addo: Partners AIDS Research Center, Harvard Medical School
Eric S. Rosenberg: Partners AIDS Research Center, Harvard Medical School
Thi Nguyen: Partners AIDS Research Center, Harvard Medical School
Rachel Allen: Cambridge University
Alicja Trocha: Partners AIDS Research Center, Harvard Medical School
Marcus Altfeld: Partners AIDS Research Center, Harvard Medical School
Suqin He: Partners AIDS Research Center, Harvard Medical School
Michael Bunce: Oxford Transplant Centre, Churchill Hospital
Robert Funkhouser: Theoretical Biology and Biophysics, Los Alamos National Laboratory
Stephen I. Pelton: Section of Pediatric Infectious Diseases, Boston Medical Center
Sandra K. Burchett: The Children's Hospital, Harvard Medical School
Kenneth McIntosh: The Children's Hospital, Harvard Medical School
Bette T. M. Korber: Theoretical Biology and Biophysics, Los Alamos National Laboratory
Bruce D. Walker: Partners AIDS Research Center, Harvard Medical School

Nature, 2001, vol. 412, issue 6844, 334-338

Abstract: Abstract 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.

Date: 2001
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DOI: 10.1038/35085576

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