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The number of CCR5 expressing CD4+ T lymphocytes is lower in HIV-infected long-term non-progressors with viral control compared to normal progressors: a cross-sectional study

BACKGROUND: The HIV co-receptors CXCR4 and CCR5 play an important role in HIV infection and replication. Therefore we hypothesize that long-term non-progressors (LTNP) with viral control have lower expression of CCR5 and CXCR4 on CD4(+) cells, specifically on memory T-lymphocytes since they are the...

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Autores principales: Meijerink, Hinta, Indrati, Agnes R, van Crevel, Reinout, Joosten, Irma, Koenen, Hans, van der Ven, Andre JAM
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271479/
https://www.ncbi.nlm.nih.gov/pubmed/25495598
http://dx.doi.org/10.1186/s12879-014-0683-0
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author Meijerink, Hinta
Indrati, Agnes R
van Crevel, Reinout
Joosten, Irma
Koenen, Hans
van der Ven, Andre JAM
author_facet Meijerink, Hinta
Indrati, Agnes R
van Crevel, Reinout
Joosten, Irma
Koenen, Hans
van der Ven, Andre JAM
author_sort Meijerink, Hinta
collection PubMed
description BACKGROUND: The HIV co-receptors CXCR4 and CCR5 play an important role in HIV infection and replication. Therefore we hypothesize that long-term non-progressors (LTNP) with viral control have lower expression of CCR5 and CXCR4 on CD4(+) cells, specifically on memory T-lymphocytes since they are the primary target cells of HIV. METHODS: In this cross-sectional study, we included five HIV-infected LTNP with viral control (CD4 > 750 cell/μl & HIV < 50 copies for ≥2 years), thirteen HIV-infected and seven HIV-uninfected individuals at Radboud UMC Nijmegen, the Netherlands. We determined the CCR5 and CXCR4 expression among CD4(+) and CD8(+) lymphocyte subsets; memory (CD45RO(+)), naïve (CD45RA(+)) cells and regulatory T-cells (CD4(+)CD25(high)FoxP3(+)). In addition, CCR5∆32 polymorphism is related with disease progression and was therefore determined using polymerase chain reaction. RESULTS: The percentage of CCR5-expressing CD4(+) cells of LTNP was comparable with healthy controls; whereas HIV-infected individuals showed more CCR5-expressing cells. This was observed in memory and naïve CD4(+) cells, but not in regulatory T-cells. The mean fluorescence intensity of CCR5-expressing CD4(+) cells was similar in all groups. All groups had comparable percentages of CXCR4-expressing cells. The mean fluorescence intensity of CXCR4-expressing cells was significantly higher in HIV-infected normally progressors in both memory and naïve CD4(+) cells, but not in CD8(+) cells. The CCR5∆32 polymorphism was not related to group. CONCLUSIONS: We show that HIV affects -directly or indirectly- the expression of CCR5 in CD4(+) T-lymphocytes; yet this effect is not seen in LTNP with viral control. Avoiding upregulation of CCR5 could be an important method via which LTNP counteracts the effects of HIV and suppresses viral replication. Exploring how LTNP suppress the upregulation of CCR5 could be an important step for discovering new therapeutics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0683-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-42714792014-12-20 The number of CCR5 expressing CD4+ T lymphocytes is lower in HIV-infected long-term non-progressors with viral control compared to normal progressors: a cross-sectional study Meijerink, Hinta Indrati, Agnes R van Crevel, Reinout Joosten, Irma Koenen, Hans van der Ven, Andre JAM BMC Infect Dis Research Article BACKGROUND: The HIV co-receptors CXCR4 and CCR5 play an important role in HIV infection and replication. Therefore we hypothesize that long-term non-progressors (LTNP) with viral control have lower expression of CCR5 and CXCR4 on CD4(+) cells, specifically on memory T-lymphocytes since they are the primary target cells of HIV. METHODS: In this cross-sectional study, we included five HIV-infected LTNP with viral control (CD4 > 750 cell/μl & HIV < 50 copies for ≥2 years), thirteen HIV-infected and seven HIV-uninfected individuals at Radboud UMC Nijmegen, the Netherlands. We determined the CCR5 and CXCR4 expression among CD4(+) and CD8(+) lymphocyte subsets; memory (CD45RO(+)), naïve (CD45RA(+)) cells and regulatory T-cells (CD4(+)CD25(high)FoxP3(+)). In addition, CCR5∆32 polymorphism is related with disease progression and was therefore determined using polymerase chain reaction. RESULTS: The percentage of CCR5-expressing CD4(+) cells of LTNP was comparable with healthy controls; whereas HIV-infected individuals showed more CCR5-expressing cells. This was observed in memory and naïve CD4(+) cells, but not in regulatory T-cells. The mean fluorescence intensity of CCR5-expressing CD4(+) cells was similar in all groups. All groups had comparable percentages of CXCR4-expressing cells. The mean fluorescence intensity of CXCR4-expressing cells was significantly higher in HIV-infected normally progressors in both memory and naïve CD4(+) cells, but not in CD8(+) cells. The CCR5∆32 polymorphism was not related to group. CONCLUSIONS: We show that HIV affects -directly or indirectly- the expression of CCR5 in CD4(+) T-lymphocytes; yet this effect is not seen in LTNP with viral control. Avoiding upregulation of CCR5 could be an important method via which LTNP counteracts the effects of HIV and suppresses viral replication. Exploring how LTNP suppress the upregulation of CCR5 could be an important step for discovering new therapeutics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0683-0) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-13 /pmc/articles/PMC4271479/ /pubmed/25495598 http://dx.doi.org/10.1186/s12879-014-0683-0 Text en © Meijerink et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Meijerink, Hinta
Indrati, Agnes R
van Crevel, Reinout
Joosten, Irma
Koenen, Hans
van der Ven, Andre JAM
The number of CCR5 expressing CD4+ T lymphocytes is lower in HIV-infected long-term non-progressors with viral control compared to normal progressors: a cross-sectional study
title The number of CCR5 expressing CD4+ T lymphocytes is lower in HIV-infected long-term non-progressors with viral control compared to normal progressors: a cross-sectional study
title_full The number of CCR5 expressing CD4+ T lymphocytes is lower in HIV-infected long-term non-progressors with viral control compared to normal progressors: a cross-sectional study
title_fullStr The number of CCR5 expressing CD4+ T lymphocytes is lower in HIV-infected long-term non-progressors with viral control compared to normal progressors: a cross-sectional study
title_full_unstemmed The number of CCR5 expressing CD4+ T lymphocytes is lower in HIV-infected long-term non-progressors with viral control compared to normal progressors: a cross-sectional study
title_short The number of CCR5 expressing CD4+ T lymphocytes is lower in HIV-infected long-term non-progressors with viral control compared to normal progressors: a cross-sectional study
title_sort number of ccr5 expressing cd4+ t lymphocytes is lower in hiv-infected long-term non-progressors with viral control compared to normal progressors: a cross-sectional study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271479/
https://www.ncbi.nlm.nih.gov/pubmed/25495598
http://dx.doi.org/10.1186/s12879-014-0683-0
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