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

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...

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Autores principales: Leslie, Alasdair, Kavanagh, Daniel, Honeyborne, Isobella, Pfafferott, Katja, Edwards, Charles, Pillay, Tilly, Hilton, Louise, Thobakgale, Christina, Ramduth, Danni, Draenert, Rika, Le Gall, Sylvie, Luzzi, Graz, Edwards, Anne, Brander, Christian, Sewell, Andrew K., Moore, Sarah, Mullins, James, Moore, Corey, Mallal, Simon, Bhardwaj, Nina, Yusim, Karina, Phillips, Rodney, Klenerman, Paul, Korber, Bette, Kiepiela, Photini, Walker, Bruce, Goulder, Philip
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213090/
https://www.ncbi.nlm.nih.gov/pubmed/15781581
http://dx.doi.org/10.1084/jem.20041455
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author Leslie, Alasdair
Kavanagh, Daniel
Honeyborne, Isobella
Pfafferott, Katja
Edwards, Charles
Pillay, Tilly
Hilton, Louise
Thobakgale, Christina
Ramduth, Danni
Draenert, Rika
Le Gall, Sylvie
Luzzi, Graz
Edwards, Anne
Brander, Christian
Sewell, Andrew K.
Moore, Sarah
Mullins, James
Moore, Corey
Mallal, Simon
Bhardwaj, Nina
Yusim, Karina
Phillips, Rodney
Klenerman, Paul
Korber, Bette
Kiepiela, Photini
Walker, Bruce
Goulder, Philip
author_facet Leslie, Alasdair
Kavanagh, Daniel
Honeyborne, Isobella
Pfafferott, Katja
Edwards, Charles
Pillay, Tilly
Hilton, Louise
Thobakgale, Christina
Ramduth, Danni
Draenert, Rika
Le Gall, Sylvie
Luzzi, Graz
Edwards, Anne
Brander, Christian
Sewell, Andrew K.
Moore, Sarah
Mullins, James
Moore, Corey
Mallal, Simon
Bhardwaj, Nina
Yusim, Karina
Phillips, Rodney
Klenerman, Paul
Korber, Bette
Kiepiela, Photini
Walker, Bruce
Goulder, Philip
author_sort Leslie, Alasdair
collection PubMed
description 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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spelling pubmed-22130902008-03-11 Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA Leslie, Alasdair Kavanagh, Daniel Honeyborne, Isobella Pfafferott, Katja Edwards, Charles Pillay, Tilly Hilton, Louise Thobakgale, Christina Ramduth, Danni Draenert, Rika Le Gall, Sylvie Luzzi, Graz Edwards, Anne Brander, Christian Sewell, Andrew K. Moore, Sarah Mullins, James Moore, Corey Mallal, Simon Bhardwaj, Nina Yusim, Karina Phillips, Rodney Klenerman, Paul Korber, Bette Kiepiela, Photini Walker, Bruce Goulder, Philip J Exp Med Article 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. The Rockefeller University Press 2005-03-21 /pmc/articles/PMC2213090/ /pubmed/15781581 http://dx.doi.org/10.1084/jem.20041455 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Leslie, Alasdair
Kavanagh, Daniel
Honeyborne, Isobella
Pfafferott, Katja
Edwards, Charles
Pillay, Tilly
Hilton, Louise
Thobakgale, Christina
Ramduth, Danni
Draenert, Rika
Le Gall, Sylvie
Luzzi, Graz
Edwards, Anne
Brander, Christian
Sewell, Andrew K.
Moore, Sarah
Mullins, James
Moore, Corey
Mallal, Simon
Bhardwaj, Nina
Yusim, Karina
Phillips, Rodney
Klenerman, Paul
Korber, Bette
Kiepiela, Photini
Walker, Bruce
Goulder, Philip
Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA
title Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA
title_full Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA
title_fullStr Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA
title_full_unstemmed Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA
title_short Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA
title_sort transmission and accumulation of ctl escape variants drive negative associations between hiv polymorphisms and hla
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213090/
https://www.ncbi.nlm.nih.gov/pubmed/15781581
http://dx.doi.org/10.1084/jem.20041455
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