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Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients

In a study of 114 epidemiologically linked Zambian transmission pairs, we evaluated the impact of human leukocyte antigen class I (HLA-I)–associated amino acid polymorphisms, presumed to reflect cytotoxic T lymphocyte (CTL) escape in Gag and Nef of the virus transmitted from the chronically infected...

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Autores principales: Goepfert, Paul A., Lumm, Wendy, Farmer, Paul, Matthews, Philippa, Prendergast, Andrew, Carlson, Jonathan M., Derdeyn, Cynthia A., Tang, Jianming, Kaslow, Richard A., Bansal, Anju, Yusim, Karina, Heckerman, David, Mulenga, Joseph, Allen, Susan, Goulder, Philip J.R., Hunter, Eric
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373834/
https://www.ncbi.nlm.nih.gov/pubmed/18426987
http://dx.doi.org/10.1084/jem.20072457
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author Goepfert, Paul A.
Lumm, Wendy
Farmer, Paul
Matthews, Philippa
Prendergast, Andrew
Carlson, Jonathan M.
Derdeyn, Cynthia A.
Tang, Jianming
Kaslow, Richard A.
Bansal, Anju
Yusim, Karina
Heckerman, David
Mulenga, Joseph
Allen, Susan
Goulder, Philip J.R.
Hunter, Eric
author_facet Goepfert, Paul A.
Lumm, Wendy
Farmer, Paul
Matthews, Philippa
Prendergast, Andrew
Carlson, Jonathan M.
Derdeyn, Cynthia A.
Tang, Jianming
Kaslow, Richard A.
Bansal, Anju
Yusim, Karina
Heckerman, David
Mulenga, Joseph
Allen, Susan
Goulder, Philip J.R.
Hunter, Eric
author_sort Goepfert, Paul A.
collection PubMed
description In a study of 114 epidemiologically linked Zambian transmission pairs, we evaluated the impact of human leukocyte antigen class I (HLA-I)–associated amino acid polymorphisms, presumed to reflect cytotoxic T lymphocyte (CTL) escape in Gag and Nef of the virus transmitted from the chronically infected donor, on the plasma viral load (VL) in matched recipients 6 mo after infection. CTL escape mutations in Gag and Nef were seen in the donors, which were subsequently transmitted to recipients, largely unchanged soon after infection. We observed a significant correlation between the number of Gag escape mutations targeted by specific HLA-B allele–restricted CTLs and reduced VLs in the recipients. This negative correlation was most evident in newly infected individuals, whose HLA alleles were unable to effectively target Gag and select for CTL escape mutations in this gene. Nef mutations in the donor had no impact on VL in the recipient. Thus, broad Gag-specific CTL responses capable of driving virus escape in the donor may be of clinical benefit to both the donor and recipient. In addition to their direct implications for HIV-1 vaccine design, these data suggest that CTL-induced viral polymorphisms and their associated in vivo viral fitness costs could have a significant impact on HIV-1 pathogenesis.
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spelling pubmed-23738342008-11-12 Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients Goepfert, Paul A. Lumm, Wendy Farmer, Paul Matthews, Philippa Prendergast, Andrew Carlson, Jonathan M. Derdeyn, Cynthia A. Tang, Jianming Kaslow, Richard A. Bansal, Anju Yusim, Karina Heckerman, David Mulenga, Joseph Allen, Susan Goulder, Philip J.R. Hunter, Eric J Exp Med Brief Definitive Reports In a study of 114 epidemiologically linked Zambian transmission pairs, we evaluated the impact of human leukocyte antigen class I (HLA-I)–associated amino acid polymorphisms, presumed to reflect cytotoxic T lymphocyte (CTL) escape in Gag and Nef of the virus transmitted from the chronically infected donor, on the plasma viral load (VL) in matched recipients 6 mo after infection. CTL escape mutations in Gag and Nef were seen in the donors, which were subsequently transmitted to recipients, largely unchanged soon after infection. We observed a significant correlation between the number of Gag escape mutations targeted by specific HLA-B allele–restricted CTLs and reduced VLs in the recipients. This negative correlation was most evident in newly infected individuals, whose HLA alleles were unable to effectively target Gag and select for CTL escape mutations in this gene. Nef mutations in the donor had no impact on VL in the recipient. Thus, broad Gag-specific CTL responses capable of driving virus escape in the donor may be of clinical benefit to both the donor and recipient. In addition to their direct implications for HIV-1 vaccine design, these data suggest that CTL-induced viral polymorphisms and their associated in vivo viral fitness costs could have a significant impact on HIV-1 pathogenesis. The Rockefeller University Press 2008-05-12 /pmc/articles/PMC2373834/ /pubmed/18426987 http://dx.doi.org/10.1084/jem.20072457 Text en © 2008 Goepfert et al. 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.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Reports
Goepfert, Paul A.
Lumm, Wendy
Farmer, Paul
Matthews, Philippa
Prendergast, Andrew
Carlson, Jonathan M.
Derdeyn, Cynthia A.
Tang, Jianming
Kaslow, Richard A.
Bansal, Anju
Yusim, Karina
Heckerman, David
Mulenga, Joseph
Allen, Susan
Goulder, Philip J.R.
Hunter, Eric
Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients
title Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients
title_full Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients
title_fullStr Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients
title_full_unstemmed Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients
title_short Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients
title_sort transmission of hiv-1 gag immune escape mutations is associated with reduced viral load in linked recipients
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373834/
https://www.ncbi.nlm.nih.gov/pubmed/18426987
http://dx.doi.org/10.1084/jem.20072457
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