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Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122323 | GEO | 2019/04/08

REPOSITORIES: GEO

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Transcriptional down-regulation of <i>ccr5</i> in a subset of HIV+ controllers and their family members.

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 RNA 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 ATAC-seq. Other nearby genes were also down-regulated, over a region of ~500 kb 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.

| S-EPMC6456299 | biostudies-literature

Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers (ATAC-Seq)

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

Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers (RNA-Seq)

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

Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers

Project description:Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers

| PRJNA504629 | ENA

CCR5 HIV controllers

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

Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers (RNA-Seq)

Project description:Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers (RNA-Seq)

| PRJNA504631 | ENA

Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers (ATAC-Seq)

Project description:Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers (ATAC-Seq)

| PRJNA504632 | ENA

CCR5 HIV controllers

Project description:CCR5 HIV controllers

| PRJEB48153 | ENA

Reduced CCR5 expression among Uganda HIV controllers.

Project description:BackgroundSeveral mechanisms including reduced CCR5 expression, protective HLA, viral restriction factors, broadly neutralizing antibodies, and more efficient T-cell responses, have been reported to account for HIV control among HIV controllers. However, no one mechanism universally accounts for HIV control among all controllers. In this study we determined whether reduced CCR5 expression accounts for HIV control among Ugandan HIV controllers. We determined CCR5 expression among Ugandan HIV controllers compared with treated HIV non-controllers through ex-vivo characterization of CD4 + T cells isolated from archived PBMCs collected from the two distinct groups.ResultsThe percentage of CCR5 + CD4 + T cells was similar between HIV controllers and treated HIV non-controllers (ECs vs. NCs, P = 0.6010; VCs vs. NCs, P = 0.0702) but T cells from controllers had significantly reduced CCR5 expression on their cell surface (ECs vs. NCs, P = 0.0210; VCs vs. NCs, P = 0.0312). Furthermore, we identified rs1799987 SNP among a subset of HIV controllers, a mutation previously reported to reduce CCR5 expression. In stark contrast, we identified the rs41469351 SNP to be common among HIV non-controllers. This SNP has previously been shown to be associated with increased perinatal HIV transmission, vaginal shedding of HIV-infected cells and increased risk of death.ConclusionCCR5 has a non-redundant role in HIV control among Ugandan HIV controllers. HIV controllers maintain high CD4 + T cells despite being ART naïve partly because their CD4 + T cells have significantly reduced CCR5 densities.

| S-EPMC10210444 | biostudies-literature

IL-15-DEPENDENT IMMUNE CROSS-TALK BETWEEN NK CELLS AND DENDRITIC CELLS IN HIV-1 ELITE CONTROLLERS

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-05 | GSE232916 | GEO