Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response


CD8+ cytotoxic T lymphocytes (CTLs) play an important role in containment of virus replication in primary human immunodeficiency virus (HIV) infection. HIV's ability to mutate to escape from CTL pressure is increasingly recognized; but comprehensive studies of escape from the CD8 T cell response in primary HIV infection are currently lacking. Here, we have fully characterized the primary CTL response to autologous virus Env, Gag, and Tat proteins in three patients, and investigated the extent, kinetics, and mechanisms of viral escape from epitope-specific components of the response. In all three individuals, we observed variation beginning within weeks of infection at epitope-containing sites in the viral quasispecies, which conferred escape by mechanisms including altered peptide presentation/recognition and altered antigen processing. The number of epitope-containing regions exhibiting evidence of early CTL escape ranged from 1 out of 21 in a subject who controlled viral replication effectively to 5 out of 7 in a subject who did not. Evaluation of the extent and kinetics of HIV-1 escape from >40 different epitope-specific CD8 T cell responses enabled analysis of factors determining escape and suggested that escape is restricted by costs to intrinsic viral fitness and by broad, codominant distribution of CTL-mediated pressure on viral replication.

Publication DOI:
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
Additional Information: J. Exp. Med. © The Rockefeller University Press. Volume 200, Number 10, November 15, 2004 1243–1256
Uncontrolled Keywords: cellular immunity,antigenic variation,hiv-1,viremia,biological models
Publication ISSN: 1540-9538
Last Modified: 08 Dec 2023 09:09
Date Deposited: 03 Feb 2015 12:20
Full Text Link:
Related URLs: http://jem.rupr ... 3.full.pdf+html (Publisher URL)
PURE Output Type: Article
Published Date: 2004-11-15
Authors: Jones, Nicola A.
Wei, Xiping
Flower, Darren R. (ORCID Profile 0000-0002-8542-7067)
Wong, MaiLee
Michor, Franziska
Saag, Michael S.
Hahn, Beatrice H.
Nowak, Martin A.
Shaw, George M.
Borrow, Persephone



Version: Published Version

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