Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs.

BACKGROUND: To address evolution of HIV-1 after transmission, we studied sequence dynamics in and outside predicted epitopes of cytotoxic T lymphocytes (CTL) in subtype B HIV-1 variants that were isolated from 5 therapy-naive horizontal HLA-disparate donor-recipient pairs from the Amsterdam Cohort S...

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Main Authors: Marjon Navis, Diana Edo Matas, Andrea Rachinger, Fransje A Koning, Peter van Swieten, Neeltje A Kootstra, Hanneke Schuitemaker
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2409968?pdf=render
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spelling doaj-26f4b54125da42c4b1dffb2f159e79a02020-11-25T01:46:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0136e242210.1371/journal.pone.0002422Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs.Marjon NavisDiana Edo MatasAndrea RachingerFransje A KoningPeter van SwietenNeeltje A KootstraHanneke SchuitemakerBACKGROUND: To address evolution of HIV-1 after transmission, we studied sequence dynamics in and outside predicted epitopes of cytotoxic T lymphocytes (CTL) in subtype B HIV-1 variants that were isolated from 5 therapy-naive horizontal HLA-disparate donor-recipient pairs from the Amsterdam Cohort Studies on HIV-1 infection and AIDS. METHODOLOGY/PRINCIPAL FINDINGS: In the first weeks after transmission, the majority of donor-derived mutations in and outside donor-HLA-restricted epitopes in Gag, Env, and Nef, were preserved in the recipient. Reversion to the HIV-1 subtype B consensus sequence of mutations in- and outside donor-HLA-restricted CTL epitopes, and new mutations away from the consensus B sequence mostly within recipient-HLA-restricted epitopes, contributed equally to the early sequence changes. In the subsequent period (1-2 years) after transmission, still only a low number of both reverting and forward mutations had occurred. During subsequent long-term follow-up, sequence dynamics were dominated by forward mutations, mostly (50-85%) in recipient-HLA-restricted CTL epitopes. At the end of long-term follow-up, on average 43% of the transmitted CTL escape mutations in donor-HLA-restricted epitopes had reverted to the subtype B consensus sequence. CONCLUSIONS/SIGNIFICANCE: The relatively high proportion of long-term preserved mutations after transmission points to a lack of back selection even in the absence of CTL pressure, which may lead to an accumulating loss of critical CTL epitopes. Our data are supportive for a continuous adaptation of HIV-1 to host immune pressures which may have implications for vaccine design.http://europepmc.org/articles/PMC2409968?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Marjon Navis
Diana Edo Matas
Andrea Rachinger
Fransje A Koning
Peter van Swieten
Neeltje A Kootstra
Hanneke Schuitemaker
spellingShingle Marjon Navis
Diana Edo Matas
Andrea Rachinger
Fransje A Koning
Peter van Swieten
Neeltje A Kootstra
Hanneke Schuitemaker
Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs.
PLoS ONE
author_facet Marjon Navis
Diana Edo Matas
Andrea Rachinger
Fransje A Koning
Peter van Swieten
Neeltje A Kootstra
Hanneke Schuitemaker
author_sort Marjon Navis
title Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs.
title_short Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs.
title_full Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs.
title_fullStr Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs.
title_full_unstemmed Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs.
title_sort molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2008-01-01
description BACKGROUND: To address evolution of HIV-1 after transmission, we studied sequence dynamics in and outside predicted epitopes of cytotoxic T lymphocytes (CTL) in subtype B HIV-1 variants that were isolated from 5 therapy-naive horizontal HLA-disparate donor-recipient pairs from the Amsterdam Cohort Studies on HIV-1 infection and AIDS. METHODOLOGY/PRINCIPAL FINDINGS: In the first weeks after transmission, the majority of donor-derived mutations in and outside donor-HLA-restricted epitopes in Gag, Env, and Nef, were preserved in the recipient. Reversion to the HIV-1 subtype B consensus sequence of mutations in- and outside donor-HLA-restricted CTL epitopes, and new mutations away from the consensus B sequence mostly within recipient-HLA-restricted epitopes, contributed equally to the early sequence changes. In the subsequent period (1-2 years) after transmission, still only a low number of both reverting and forward mutations had occurred. During subsequent long-term follow-up, sequence dynamics were dominated by forward mutations, mostly (50-85%) in recipient-HLA-restricted CTL epitopes. At the end of long-term follow-up, on average 43% of the transmitted CTL escape mutations in donor-HLA-restricted epitopes had reverted to the subtype B consensus sequence. CONCLUSIONS/SIGNIFICANCE: The relatively high proportion of long-term preserved mutations after transmission points to a lack of back selection even in the absence of CTL pressure, which may lead to an accumulating loss of critical CTL epitopes. Our data are supportive for a continuous adaptation of HIV-1 to host immune pressures which may have implications for vaccine design.
url http://europepmc.org/articles/PMC2409968?pdf=render
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