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MicroRNAs differentially present in the plasma of HIV elite controllers

ABSTRACT: Elite controllers maintain HIV-1 viral loads below the limit of detection. The mechanisms responsible for this phenomenon are poorly understood. As microRNAs (miRNAs) are regulators of gene expression and some of them modulate HIV infection, we have studied the miRNA profile in plasma from HIV elite controllers and chronically infected individuals and compared against healthy donors. Several miRNAs correlate with CD4+ T cell count or with the known time of infection. No significant differences were observed between elite controllers and healthy donors; however, 16 miRNAs were different in the plasma of chronic infected versus healthy donors. In addition, levels of hsa-miR-29b-3p, hsa-miR-33a-5p and hsa-miR-146a-5p were higher in plasma from elite controllers than chronic infected and hsa-miR-29b-3p and hsa-miR-33a-5p overexpression significantly reduced the viral production in MT2 cells. Therefore, levels of circulating miRNAs might be of diagnostic and/or prognostic value for HIV infection. Additionally, hsa-miR-29b-3p and miR-33a-5p may be used in therapeutic strategies. An exploratory cross-sectional study of microRNA levels in EDTA plasma samples. Plasma samples were obtained from 24 subjects and were classified in 3 groups, 9 Elite Controllers (defined as individuals with plasma viral load (PVL) < 50 copies/ml, CD4 count >350/ml), 9 chronic HIV patients (CH) under anti-retroviral treatment and 6 healthy HIV negative donors (HD). This study was approved by the HuM-CM-)sped Foundation Ethics Committee and informed consent was obtained from all subjects.

ORGANISM(S): Homo sapiens

SUBMITTER: Matthias Hackl

PROVIDER: E-GEOD-58868 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MicroRNAs differentially present in the plasma of HIV elite controllers

Project description:Elite controllers maintain HIV-1 viral loads below the limit of detection. The mechanisms responsible for this phenomenon are poorly understood. As microRNAs (miRNAs) are regulators of gene expression and some of them modulate HIV infection, we have studied the miRNA profile in plasma from HIV elite controllers and chronically infected individuals and compared against healthy donors. Several miRNAs correlate with CD4+ T cell count or with the known time of infection. No significant differences were observed between elite controllers and healthy donors; however, 16 miRNAs were different in the plasma of chronic infected versus healthy donors. In addition, levels of hsa-miR-29b-3p, hsa-miR-33a-5p and hsa-miR-146a-5p were higher in plasma from elite controllers than chronic infected and hsa-miR-29b-3p and hsa-miR-33a-5p overexpression significantly reduced the viral production in MT2 cells. Therefore, levels of circulating miRNAs might be of diagnostic and/or prognostic value for HIV infection. Additionally, hsa-miR-29b-3p and miR-33a-5p may be used in therapeutic strategies.

2014-08-04 | GSE58868 | GEO

TaqMan Peripheral blood mononuclear cell miRNA profiles of HIV-1 infected elite controllers, viremic patients, treated patients and uninfected control donors

Project description:Background: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers. Results: After adequate normalization, expression profile of 286 human miRNAs (hsa-miR) was evaluated in 29 individuals classified in 4 groups: 8 elite controllers (EC; viral load <50 cp/ml without treatment), 8 viremic progressors (VP; VL>5000 cp/ml without treatment), 8 patients under antiretroviral treatment (ART; VL<200cp/ml) and 5 uninfected individuals (HIV-) through TaqMan® Array Human microRNA Cards v3.0. A differential expression pattern consisting of 23 miRNAs overcame significantly different when comparing EC and VP. Profiling analysis segregated the population in two different blocks: while EC and HIV- clustered together in the same block (EC/HIV-_block 1), VP and ART individuals clustered together in a second block (VP/ART_block 2). Two inversely expressed miRNA patterns were determined within those two blocks: a set of 4 miRNAs (hsa-miR-221, -27a, -27b and -29b) was up-expressed in EC/HIV-_block and down-expressed in VP/ART_block while 19 miRNAs were down-expressed in block 1 and up-expressed in block 2. Differential miRNAs were successfully validated through individual RT-qPCR assays. Conclusions: Profile in EC resembled HIV- and differentially clusters with VP and ART. Therefore, differential clustering does not rely on undetectable viremia. Peripheral blood mononuclear cell samples were from five uninfected controls, eight viremic HIV-1-infected patients, eight HIV-1 elite controllers with undetectable viral load and eight HIV-1antiretroviral treated individuals with undetectable viral load.

2014-05-06 | E-GEOD-57323 | biostudies-arrayexpress

microRNA Expression Profile on Stimulated Peripheral Blood Mononuclear Cells from HIV-1 infected Elite Controllers, Viremic Patients, Treated Patients and Uninfected Donors

Project description:Background: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers Results: After adequate normalization, expression profile of 286 human miRNAs (hsa-miR) was evaluated in phytohaemagglutinin-stimulated PBMCs from 29 individuals classified in 4 groups: 8 elite controllers (EC; viral load <50 cp/ml without treatment), 8 viremic progressors (VP; VL>5000 cp/ml without treatment), 8 patients under antiretroviral treatment (ART; VL<200cp/ml) and 5 uninfected individuals (HIV-) through TaqMan® Array Human microRNA Cards v3.0. A differential expression pattern consisting of 23 miRNAs overcame significantly different when comparing EC and VP. Profiling analysis segregated the population in two different blocks: while EC and HIV- clustered together in the same block (EC/HIV-_block 1), VP and ART individuals clustered together in a second block (VP/ART_block 2). Two inversely expressed miRNA patterns were determined within those two blocks: a set of 4 miRNAs (hsa-miR-221, -27a, -27b and -29b) was up-expressed in EC/HIV-_block and down-expressed in VP/ART_block while 19 miRNAs were down-expressed in block 1 and up-expressed in block 2. Differential miRNAs were successfully validated through individual RT-qPCR assays. Conclusions: Profile in EC resembled HIV- and differentially clusters with VP and ART. Therefore, differential clustering does not rely on undetectable viremia.

2014-05-06 | GSE57323 | GEO

Small RNA-seq analysis of circulating miRNAs to identify phenotypic variability in Friedreich's ataxia patients

Project description:Friedreich’s ataxia (FRDA; OMIM 229300), an autosomal recessive neurodegenerative mitochondrial disease, is the most prevalent hereditary ataxia. In addition, FRDA patients showed additional non-neurological features such as scoliosis, diabetes and cardiac complications. Hypertrophic cardiomyopathy, which is found in two thirds of patients at the time of diagnosis, is the primary cause of death in these patients. In this data set, using small RNA-sequencing of small RNA purified from plasma samples of FRDA patients and controls we identified differential expression of miRNAs (hsa-miR-128-3p, hsa-miR-625-3p, hsa-miR-130b-5p, hsa-miR-151a-5p, hsa-miR-330-3p, hsa-miR-323a-3p, and hsa-miR-142-3p) between both groups. In addition, we found that miR-323a-3p can be used as a biomarker for differentiation of FRDA patients with cardiac problems. Identification of miRNA signatures could therefore provide new molecular explanation for pathological mechanisms occurring during the natural history of the FRDA. Since miRNA levels change with disease progression and pharmacological interventions, miRNAs will contribute to design new therapeutic strategies and improve clinical decisions. Plama miRNA profiles of 25 Friedreich's ataxia patients and 17 healthy subjects were generated by deep sequencing using Illumina HiScan SQ.

2017-10-18 | E-GEOD-105052 | biostudies-arrayexpress

Transcriptional profiling of CD4 T-cells in HIV-1 infected patients

2011-01-01 | GSE23879 | GEO

Epigenome analysis in several cohorts of HIV progession and in uninfected individuals

Project description:Genome wide DNA methylation profiling of CD4 T cells from uninfected and HIV-infected individuals (viremic, ART-suppressed and elite controllers [EC]) The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 485,577 CpGs in DNA from peripheral CD4 T cells samples. Samples included: 22 from HIV-uninfected individuals (uninfected group), 42 from HIV-infected individuals (21 from HIV-infected viremic (viremic group) and 21 from the same participants after viral suppression (viral load< 50 copies HIV-1 RNA/plasma) by antiretroviral therapy administrarion (ART group), and 21 from elite controllers (EC group)

2023-01-16 | GSE143942 | GEO

Transcriptional profiling of CD4 T-cells in HIV-1 infected patients

Project description:HIV-1 elite controllers maintain undetectable levels of viral replication in the absence of antiretroviral therapy, but their underlying immunological and virological characteristics may vary. Here, we used a whole-genome transcriptional profiling approach to characterize gene expression signatures of CD4 T cells from an unselected cohort of elite controllers. In the majority of elite controllers, transcriptional profiles were similar to HAART-treated patients, while being different from HIV-1 negative persons. Yet, a smaller proportion of elite controllers showed an opposite gene expression pattern that was indistinguishable from HIV-1 negative persons, but different from HAART-treated individuals. Elite controllers with this gene expression signature had significantly higher CD4 T cell counts, smaller levels of HIV-1-specific CD8+ T cell responses and tended to have lower residual HIV-1 viremia as determined by ultra-sensitive single-digit PCR, but did not differ from other elite controllers in terms of HLA class I alleles, age or sex. Thus, these data identify a specific subgroup of elite controllers whose clinical, immunological and gene expression characteristics approximate those of HIV-1 negative persons. PBMC from study persons were stained with monoclonal antibodies against CD3, CD4 and HLA-DR, and subsequently subjected to live sorting at 70 psi using an ARIA cell sorting device (Becton Dickinson) located in a specifically designated biosafety cabinet. Following mRNA extraction form the sorted cells (RNAeasy kit, Qiagen), whole genome transcriptional profiling was performed using WG-DASL microarrays (Illumina) according to standard protocols. We included an unselected cohort of elite controllers (n = 12) and two background populations of HIV-1 negative persons (n = 9) and HIV-1 infected persons effectively treated with HAART (n = 14). Four replicates were included in the study.

2011-01-01 | E-GEOD-23879 | biostudies-arrayexpress

Expression analysis of microRNAs in plasma of new HIV-infected cases, old HIV-infected cases and healthy controls.

Project description:There are 19 differentially expressed microRNAs among new HIV-infected cases, old HIV-infected cases and healthy controls. Five microRNAs show trends in healthy controls, new HIV-infected cases and old HIV-infected cases, they are hsa-miR-1291, and hsa-miR-3609 with up-trends, and hsa-miR-3162-3p, hsa-miR-874-5p and hsa-miR-4258 with down-trends.

2017-12-01 | GSE103555 | GEO

Gene expression analysis of THP-1 cells (monocytic cell line) transfected with microRNA mimics: let-7d-5p, miR-27b-3p, miR-151a-5p.

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2023-02-06 | GSE217969 | GEO

Gene expression analysis of THP-1 cells (monocytic cell line) transfected with microRNA mimics: let-7d-3p, let-7e-5p,miR-146a-5p,miR-130a-3p, miR-151a-3p.

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2023-02-06 | GSE217971 | GEO

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