Loading...
Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA
Leslie, A Kavanagh, D Honeyborne, I Pfafferott, K Edwards, C Pillay, T Hilton, L Thobakgale, C Ramduth, D Draenert, R
Leslie, A
Kavanagh, D
Honeyborne, I
Pfafferott, K
Edwards, C
Pillay, T
Hilton, L
Thobakgale, C
Ramduth, D
Draenert, R
Authors
Editors
Other contributors
Affiliation
Epub Date
Issue Date
2005-03-21
Submitted date
Subjects
Alternative
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.
Citation
Leslie, A., Kavanagh, D., Honeyborne, I. et al. (2005) Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA, Journal of Experimental Medicine, 201 (6): 891–902.
Publisher
Journal
Research Unit
PubMed ID
15781581 (pubmed)
PubMed Central ID
Embedded videos
Type
Journal article
Language
en
Description
© 2005 The Authors. Published by Rockefeller University Press. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1084/jem.20041455
Series/Report no.
ISSN
0022-1007
EISSN
1540-9538
ISBN
ISMN
Gov't Doc #
Sponsors
This work was supported by the National Institutes of Health (contract N01-Al-15422 [“HLA typing and CTL epitope mapping to guide HIV vaccine development”] and AI46995-01A1), the Wellcome Trust (to P. Goulder and A. Leslie), the Elizabeth Glaser Pediatric AIDS Foundation (to P. Goulder), and the Doris Duke Charitable Foundation.
Rights
Licence for published version: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International