Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Leslie, AKavanagh, D
Honeyborne, I
Pfafferott, K
Edwards, C
Pillay, T
Hilton, L
Thobakgale, C
Ramduth, D
Draenert, R
Le Gall, S
Luzzi, G
Edwards, A
Brander, C
Sewell, AK
Moore, S
Mullins, J
Moore, C
Mallal, S
Bhardwaj, N
Yusim, K
Phillips, R
Klenerman, P
Korber, B
Kiepiela, P
Walker, B
Goulder, P
Issue Date
2005-03-21
Metadata
Show full item recordAbstract
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
Rockefeller University PressJournal
Journal of Experimental MedicinePubMed ID
15781581 (pubmed)Additional Links
https://rupress.org/jem/article/201/6/891/52735/Transmission-and-accumulation-of-CTL-escapeType
Journal articleLanguage
enDescription
© 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.20041455ISSN
0022-1007EISSN
1540-9538Sponsors
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.ae974a485f413a2113503eed53cd6c53
10.1084/jem.20041455
Scopus Count
Collections
Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
Related articles
- Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA.
- Authors: Leslie A, Kavanagh D, Honeyborne I, Pfafferott K, Edwards C, Pillay T, Hilton L, Thobakgale C, Ramduth D, Draenert R, Le Gall S, Luzzi G, Edwards A, Brander C, Sewell AK, Moore S, Mullins J, Moore C, Mallal S, Bhardwaj N, Yusim K, Phillips R, Klenerman P, Korber B, Kiepiela P, Walker B, Goulder P
- Issue date: 2005 Mar 21
- Identification of HLA class I-associated amino acid polymorphisms in the HIV-1C proteome.
- Authors: Boutwell CL, Essex M
- Issue date: 2007 Jan
- Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1.
- Authors: Brumme ZL, Brumme CJ, Heckerman D, Korber BT, Daniels M, Carlson J, Kadie C, Bhattacharya T, Chui C, Szinger J, Mo T, Hogg RS, Montaner JS, Frahm N, Brander C, Walker BD, Harrigan PR
- Issue date: 2007 Jul
- Marked epitope- and allele-specific differences in rates of mutation in human immunodeficiency type 1 (HIV-1) Gag, Pol, and Nef cytotoxic T-lymphocyte epitopes in acute/early HIV-1 infection.
- Authors: Brumme ZL, Brumme CJ, Carlson J, Streeck H, John M, Eichbaum Q, Block BL, Baker B, Kadie C, Markowitz M, Jessen H, Kelleher AD, Rosenberg E, Kaldor J, Yuki Y, Carrington M, Allen TM, Mallal S, Altfeld M, Heckerman D, Walker BD
- Issue date: 2008 Sep