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 inverted question mark> inverted question mark750cell/ inverted question markl & HIV inverted question mark< inverted question mark50 copies for inverted question mark2 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+), naive (CD45RA+) cells and regulatory T-cells (CD4+CD25highFoxP3+). In addition, CCR5 inverted question mark32 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 naive 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 naive CD4+ cells, but not in CD8+ cells. The CCR5 inverted question mark32 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.
