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Abstract
BackgroundThe 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.MethodsIn 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+CD25highFoxP3+). In addition, CCR5∆32 polymorphism is related with disease progression and was therefore determined using polymerase chain reaction.ResultsThe 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.ConclusionsWe 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 materialThe online version of this article (doi:10.1186/s12879-014-0683-0) contains supplementary material, which is available to authorized users.
Highlights
The Human immunodeficiency virus (HIV) co-receptors CXCR4 and CCR5 play an important role in HIV infection and replication
Memory T-lymphocytes are preferentially targeted by HIV, whereas increased numbers of regulatory T-cells are associated with disease progression [3]
The characteristics of the subjects are shown in Table 1; as expected the median CD4 cells were higher and the viral load was lower in HIV-infected long-term non-progressors (LTNP) than in normal progressors
Summary
The HIV co-receptors CXCR4 and CCR5 play an important role in HIV infection and replication. Resting CD4+ T-lymphocytes are a reservoir of HIV infection; subsets of these lymphocytes are differentially affected by HIV and subdividing these cells in memory and naïve cells can provide better understanding of their individual roles [1,2]. Memory T-lymphocytes are preferentially targeted by HIV, whereas increased numbers of regulatory T-cells are associated with disease progression [3]. The X4 variants, that utilize CXCR4, are mostly detectible at a late stage of the disease and in only up to 50% of all patients [6]. Both co-receptors are expressed on leukocytes, but to different extents on different T-cell subsets [7,8]. Activated CD4+CCR5+ T-lymphocytes are the primary target and an optimal subset for virus replication [2]
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