Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA

A. Leslie; D. Kavanagh; I. Honeyborne; K. Pfafferott; C. Edwards; T. Pillay; L. Hilton; C. Thobakgale; D. Ramduth; R. Draenert; S. Le Gall; G. Luzzi; A. Edwards; C. Brander; A.K. Sewell; S. Moore; J. Mullins; C. Moore; S. Mallal; N. Bhardwaj; K. Yusim; R. Phillips; P. Klenerman; B. Korber; P. Kiepiela; B. Walker; P. Goulder

doi:10.1084/jem.20041455

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Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA

Journal article

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Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA

A. Leslie, D. Kavanagh, I. Honeyborne, K. Pfafferott, C. Edwards, T. Pillay, L. Hilton, C. Thobakgale, D. Ramduth, R. Draenert, …

Journal of Experimental Medicine, Vol.201(6), pp.891-902

2005

DOI: https://doi.org/10.1084/jem.20041455

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Abstract

Human immunodeficiency virus (HIV)-1 amino acid sequence polymorphisms associated with expression of specific human histocompatibility leukocyte antigen (HLA) class I alleles suggest sites of cytotoxic T lymphocyte (CTL)-mediated selection pressure and immune escape. The associations most frequently observed are between expression of an HLA class I molecule and variation from the consensus sequence. However, a substantial number of sites have been identified in which particular HLA class I allele expression is associated with preservation of the consensus sequence. The mechanism behind this is so far unexplained. The current studies, focusing on two examples of “negatively associated” or apparently preserved epitopes, suggest an explanation for this phenomenon: negative associations can arise as a result of positive selection of an escape mutation, which is stable on transmission and therefore accumulates in the population to the point at which it defines the consensus sequence. Such negative associations may only be in evidence transiently, because the statistical power to detect them diminishes as the mutations accumulate. If an escape variant reaches fixation in the population, the epitope will be lost as a potential target to the immune system. These data help to explain how HIV is evolving at a population level. Understanding the direction of HIV evolution has important implications for vaccine development.

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Title: Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA
Authors/Creators: A. Leslie (Author/Creator)
D. Kavanagh (Author/Creator)
I. Honeyborne (Author/Creator)
K. Pfafferott (Author/Creator)
C. Edwards (Author/Creator)
T. Pillay (Author/Creator)
L. Hilton (Author/Creator)
C. Thobakgale (Author/Creator)
D. Ramduth (Author/Creator)
R. Draenert (Author/Creator)
S. Le Gall (Author/Creator)
G. Luzzi (Author/Creator)
A. Edwards (Author/Creator)
C. Brander (Author/Creator)
A.K. Sewell (Author/Creator)
S. Moore (Author/Creator)
J. Mullins (Author/Creator)
C. Moore (Author/Creator)
S. Mallal (Author/Creator)
N. Bhardwaj (Author/Creator)
K. Yusim (Author/Creator)
R. Phillips (Author/Creator)
P. Klenerman (Author/Creator)
B. Korber (Author/Creator)
P. Kiepiela (Author/Creator)
B. Walker (Author/Creator)
P. Goulder (Author/Creator)
Publication Details: Journal of Experimental Medicine, Vol.201(6), pp.891-902
Publisher: The Rockefeller University Press
Identifiers: 991005544656407891
Murdoch Affiliation: Centre for Clinical Immunology and Biomedical Statistics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.46 HIV Pathogenesis
Web Of Science research areas: Immunology; Medicine, Research & Experimental
ESI research areas: Immunology