The HIV co-receptor CCR5, regulates the cellular architecture of osteoclast
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PROVIDER: PRJNA416058 | ENA |
REPOSITORIES: ENA
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Project description:C-C chemokine receptor 5 (CCR5) is a co-receptor of HIV. Its ligand, CCL5 significantly augmented the number of wild-type osteoclasts but not Ccr5-deficient cells, indicating that CCL5 enhanced RANKL-induced osteoclastogenesis through CCR5. To investigate the changes in the transcriptional signatures induced by CCL5 in osteoclastogenesis, cultured osteoclasts at pOC stages were incubated with or without rmCCL5 for 2 days, and then subjected for RNA sequencing.
2017-11-15 | GSE106259 | GEO
Project description:Sequencing of 9kb of the CCR5 genomic locus in 15 patients who naturally control HIV infection
2021-12-07 | E-MTAB-11062 | biostudies-arrayexpress
Project description:CCR5 is the main HIV co-receptor. We aimed to (1) compare CCR5 expression on immune cells between people living with HIV (PLHIV) using combination antiretroviral therapy (cART) and HIV-uninfected controls, (2) relate CCR5 expression to viral reservoir size and (3) assess detereminants of CCR5 expression. Percentages of CCR5 positive cells (%) and CCR5 mean fluorescence intensity (MFI) assessed by flow cytometry in monocytes and lymphocyte subsets were correlated to host factors, HIV-1 cell-associated (CA)-RNA and CA-DNA, plasma inflammation markers and metabolites.
2022-08-12 | PXD031628 | Pride
Project description:HIV-1 usually utilize CCR5 as the co-receptor and rarely switches to CXCR4-tropic until late stage of infection. CCR5+CD4+ T cells are the major virus-producing cells in patients as well as SIV-infected non-human primates. The differentiation of CCR5+CD4+ T cells is associated with the availability of IL-15, which increases during acute HIV-1 infection. Here, we report that CCR5 is expressed by CD4+ T cells exhibiting effector or effector memory phenotype with high expression levels of the IL-2/IL-15 receptor common beta and gamma chains. IL-15 but not IL-7 improves the survival of CCR5+CD4+ T cells, drives their expansion, and facilitates HIV-1 infection in vitro and in humanized mice. Our study suggests that IL-15 plays confounding roles in HIV-1 infection, and future studies on the IL-15-based boosting of anti-HIV-1 immunity should carefully exam the potential effects on the expansion of HIV-1 reservoirs in CCR5+CD4+ T cells.
2022-04-03 | GSE199729 | GEO
Project description:The chemokine receptor CCR5 is a major co-receptor for human immunodeficiency virus 1 (HIV-1) mediating infection of target cells1,2. Beyond its function as co-receptor, CCR5 also influences the course of HIV disease and progression to AIDS3. However, it is unclear how CCR5 affects HIV-associated damage to the central nervous system (CNS) and development of HIV-associated neurocognitive disorders (HAND) independently of its co-receptor function. Here we show in a transgenic model of brain damage induced by HIV envelope protein gp1204 that genetic ablation of CCR5 prevents neuronal injury and loss and limits microglial activation, but fails to abrogate astrocytosis. CCR5 deficiency also protected gp120-transgenic mice against impairment of spatial learning and memory. Thus, CCR5-deficiency revealed that astrocytosis, a prominent pathological feature of AIDS brains5, can occur independently from neuronal demise and behavioral impairment. Since the viral envelope protein expressed in the transgenic mouse model originated from HIV-1 LAV4, a CXCR4-preferring virus that can infect macrophages6, CCR5 appeared to exert its control of neuronal injury predominantly in an indirect fashion and independently from its function as a co-receptor. Using analysis of genome-wide CNS gene expression we identified a subset of 734 genes that were differentially regulated in association with neuronal injury in the presence of CCR5. This subset of genes indicated that neuronal injury was associated with activation of macrophages and microglia. A set of 1305 genes was only differentially regulated in association with gp120 in the absence of CCR5 and indicated changes to leukocyte function and the anti-viral immune response besides a down-regulation of components in the GABAergic neurotransmission system. Interestingly, the most significantly differentially expressed genes were observed in a separate subset of 461 genes that was regulated in association with gp120 but independently of the CCR5 genotype. The finding that differential regulation of the 461 and 1305 gene sets was not necessarily linked to neuronal damage and loss suggested that altered expression of at least some of these factors may represent a protective adaptive response of the brain to the presence of viral gp120. Additional experiments using quantitative RT-PCR, protein assays and flow cytometry further supported the notion that CCR5 deficiency blunted microglial activation, a hallmark of HIV-associated brain injury7-9 without significantly affecting the expression of viral gp120. These results provide in vivo evidence for a significant role of CCR5 in HIV-associated CNS injury and behavioral impairment that is independent of the molecules’ function as HIV co-receptor. To characterize the neuroprotective effect of CCR5 ablation in the presence of HIV gp120, we next performed a genome-wide gene expression analysis using whole brain RNA preparations of mice from lines 1 and 2. We decided to collect samples from two time points before and after the ages of when we analyzed histopathology (6 months) and behavior (8 to 9 months) in order to identify genes for which differential regulation may be affected by an interaction of HIVgp120 expression and age. Accordingly, we collected brain tissue of gp120tg, CCR5KO x gp120tg, WT and CCR5KO mice at five different ages: 1.5, 3, 6, 12, and 20 (line 1) or 16 (line 2) months.
2014-09-09 | E-GEOD-47029 | biostudies-arrayexpress
Project description:Hematopoietic stem cell transplantation from a donor whose T cells did not express CCR5—a co-receptor for HIV—resulted in an apparent cure of an HIV-infected adult1. Herein, we have exploited this strategy by adoptive transfer of autologous CCR5 gene disrupted CD4+ T cells (SB-728-T) in 9 HIV+ participants. A single infusion of SB-728-T, a minimally invasive intervention, led to sustained increases in CD4+ T cell counts through 3.5 years (33-44 months) compared to baseline (median increase of +193 cells/µl, P = 0.02). The degree of long-term immune reconstitution was associated with expansion of a polyclonal stem cell-like CCR5-depleted CD4+ T cell population. SB-728-T therapy was also associated with expansion of polyfunctional HIV-specific CD8+ T cells (P = 0.03) and decline in size of the HIV reservoir (-0.23 to -3.6 log decrease). Collectively, these data suggest that generation and protection of CD4 memory cells will improve T cell homeostasis, enhance HIV-specific immunity, and accelerate the decline of the host HIV reservoir.
2016-02-01 | GSE66214 | GEO
Project description:The chemokine receptor CCR5 is a major co-receptor for human immunodeficiency virus 1 (HIV-1) mediating infection of target cells1,2. Beyond its function as co-receptor, CCR5 also influences the course of HIV disease and progression to AIDS3. However, it is unclear how CCR5 affects HIV-associated damage to the central nervous system (CNS) and development of HIV-associated neurocognitive disorders (HAND) independently of its co-receptor function. Here we show in a transgenic model of brain damage induced by HIV envelope protein gp1204 that genetic ablation of CCR5 prevents neuronal injury and loss and limits microglial activation, but fails to abrogate astrocytosis. CCR5 deficiency also protected gp120-transgenic mice against impairment of spatial learning and memory. Thus, CCR5-deficiency revealed that astrocytosis, a prominent pathological feature of AIDS brains5, can occur independently from neuronal demise and behavioral impairment. Since the viral envelope protein expressed in the transgenic mouse model originated from HIV-1 LAV4, a CXCR4-preferring virus that can infect macrophages6, CCR5 appeared to exert its control of neuronal injury predominantly in an indirect fashion and independently from its function as a co-receptor. Using analysis of genome-wide CNS gene expression we identified a subset of 734 genes that were differentially regulated in association with neuronal injury in the presence of CCR5. This subset of genes indicated that neuronal injury was associated with activation of macrophages and microglia. A set of 1305 genes was only differentially regulated in association with gp120 in the absence of CCR5 and indicated changes to leukocyte function and the anti-viral immune response besides a down-regulation of components in the GABAergic neurotransmission system. Interestingly, the most significantly differentially expressed genes were observed in a separate subset of 461 genes that was regulated in association with gp120 but independently of the CCR5 genotype. The finding that differential regulation of the 461 and 1305 gene sets was not necessarily linked to neuronal damage and loss suggested that altered expression of at least some of these factors may represent a protective adaptive response of the brain to the presence of viral gp120. Additional experiments using quantitative RT-PCR, protein assays and flow cytometry further supported the notion that CCR5 deficiency blunted microglial activation, a hallmark of HIV-associated brain injury7-9 without significantly affecting the expression of viral gp120. These results provide in vivo evidence for a significant role of CCR5 in HIV-associated CNS injury and behavioral impairment that is independent of the molecules’ function as HIV co-receptor.
2014-09-09 | GSE47029 | GEO
Project description:HIV+ Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4+ T cells with resistance specific to R5-tropic HIV, reversed after introduction of CCR5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4+ T cells of these EC/VCs had lower CCR2 and CCR5 mRNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of CCR2 and CCR5, despite having more accessible chromatin by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq). Other nearby genes were also down-regulated, over a region of ~500kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with CCR2/CCR5 down-regulation, suggesting that the phenotype is heritable.
2019-04-08 | GSE122322 | GEO
Project description:HIV+ Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4+ T cells with resistance specific to R5-tropic HIV, reversed after introduction of CCR5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4+ T cells of these EC/VCs had lower CCR2 and CCR5 mRNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of CCR2 and CCR5, despite having more accessible chromatin by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq). Other nearby genes were also down-regulated, over a region of ~500kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with CCR2/CCR5 down-regulation, suggesting that the phenotype is heritable.
2019-04-08 | GSE122321 | GEO