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

Nicola A. Jones, Xiping Wei, Darren R. Flower, MaiLee Wong, Franziska Michor, Michael S. Saag, Beatrice H. Hahn, Martin A. Nowak, George M. Shaw, Persephone Borrow

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)1243-1256
Number of pages14
JournalJournal of Experimental Medicine
Volume200
Issue number10
DOIs
Publication statusPublished - 15 Nov 2004

Fingerprint

Cytotoxic T-Lymphocytes
HIV-1
Epitopes
HIV
Virus Diseases
tat Gene Products
env Gene Products
T-Lymphocytes
gag Gene Products
Pressure
Antigen Presentation
Virus Replication
Statistical Factor Analysis
Viruses
Costs and Cost Analysis
Peptides
Infection

Bibliographical note

J. Exp. Med. © The Rockefeller University Press. Volume 200, Number 10, November 15, 2004 1243–1256

Keywords

  • cellular immunity
  • antigenic variation
  • hiv-1
  • viremia
  • biological models

Cite this

Jones, Nicola A. ; Wei, Xiping ; Flower, Darren R. ; Wong, MaiLee ; Michor, Franziska ; Saag, Michael S. ; Hahn, Beatrice H. ; Nowak, Martin A. ; Shaw, George M. ; Borrow, Persephone. / Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response. In: Journal of Experimental Medicine . 2004 ; Vol. 200, No. 10. pp. 1243-1256.
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Jones, NA, Wei, X, Flower, DR, Wong, M, Michor, F, Saag, MS, Hahn, BH, Nowak, MA, Shaw, GM & Borrow, P 2004, 'Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response', Journal of Experimental Medicine , vol. 200, no. 10, pp. 1243-1256. https://doi.org/10.1084/jem.20040511

Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response. / Jones, Nicola A.; Wei, Xiping ; Flower, Darren R.; Wong, MaiLee; Michor, Franziska; Saag, Michael S.; Hahn, Beatrice H.; Nowak, Martin A.; Shaw, George M.; Borrow, Persephone.

In: Journal of Experimental Medicine , Vol. 200, No. 10, 15.11.2004, p. 1243-1256.

Research output: Contribution to journalArticle

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