MiRNA profiling of CD4+ T cells in chronically infected HIV-1 patients, LTNPs and healthy controls
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE24022 | GEO | 2012/05/22
SECONDARY ACCESSION(S): PRJNA130267
REPOSITORIES: GEO
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Project description:We extracted total RNA from CD4+ T cells from 3 patient groups: chronic HIV-1 patients (CHI), long term non-progressors (LTNPs) and healthy controls (HC). Array results show that a large number of miRNAs are altered in HIV-1 infected patients compared to HC. Most of the differentially expressed miRNAs are down-regulated but there are some up-regulated miRNAs. A particular family of miRNAs which appear to be downregulated in HIV-1 infected patients is the let-7 family of miRNAs. In this study, we have included 8 healthy controls, 7 LTNPs and 7 CHI patients. We extracted RNA from magnetically separated CD4+ T cells (separated from peripheral blood mononuclear cells) and ran them on an Agilent miRNA array.
2012-05-21 | E-GEOD-24022 | biostudies-arrayexpress
Project description:The relationship between host microRNAs (miRNA), viral control and immune response has not been elucidated in the field of HIV yet. The aim of this study was to assess the differential miRNA profile in CD8+ T-cells between HIV-infected individuals who differ in terms of disease progression. A total of 136 RNAs (miRNAs) were analyzed: 68 RNAs from resting CD8+ T-cells and the respective 68 RNAs from stimulated CD8+ T-cells from Elite Controllers (EC, n=15), Viremic Controllers (VC, n=15), Viremic Progressors (VP, n=13), Treated Patients (ART, n=14) and Uninfect Donors (HIV-, n=11).
2015-08-04 | E-GEOD-71650 | biostudies-arrayexpress
Project description:Human immunodeficiency virus type 1 (HIV-1)-induced inflammation and/or long-term antiretroviral drug toxicity may contribute to the evolution of liver disease. We investigated circulating plasma microRNAs (miRNAs) as potential biomarkers of liver injury in patients mono-infected with HIV-1. We performed large-scale deep sequencing analyses of small RNA level on plasma samples from patients with HIV-1 mono-infection that had elevated or normal levels of alanine aminotransferase (ALT) or focal nodular hyperplasia (FNH). Hepatitis C virus (HCV) mono-infected patients were also studied. Compared to healthy donors, patients with HIV-1 or HCV mono-infections showed significantly altered (fold change >2, adjusted p<0.05) level of 25 and 70 miRNAs, respectively. Of the 25 altered miRNAs found in patients with HIV-1, 19 were also found in patients mono-infected with HCV. Moreover, 13 of the 14 most up-regulated miRNAs (range: 9.3-3.4-fold increase) in patients with HCV mono-infections were also up-regulated in patients with HIV-1 mono-infections. Importantly, most of these miRNAs significantly and positively correlated with ALT and aspartate aminotransferase (AST) levels, and liver fibrosis stage (p<0.05). MiR-122-3p and miR-193b-5p were highly up-regulated HIV-1 mono-infected patients with elevated ALT or FNH, but not in HIV-1 patients with normal levels of ALT. These results reveal that HIV-1 infections impacted liver-related miRNA levels in the absence of an HCV co-infection, which highlights the potential of miRNAs as biomarkers for the progression of liver injury in HIV-1 infected patients.
2019-12-06 | GSE141522 | GEO
Project description:HIV-infected long-term non-progressors (LTNPs) are a special group of people who can naturally control HIV and maintain good host immunity. Their mechanism is related to viruses, host genetic characteristics, immune response and other factors, but the relationship between the activation level of innate immunity and long-term non-progression is not clear. Therefore,we hypothesize that LTNPs may have some founction to control the HIV replication in vivo.In this study, we used RNA-seq to investigate the transcription（lncRNA, miRNA and mRNA) profiles of LTNPs and typical progressors (TPs).This study is showing expression spectrum of mRNA and non-coding RNA between HIV-infected long-term non-progressors and typical progressors, and analyze the role of mRNA,IncRNA and miRNA in the HIV infected long-term non-progression based on whole transcriptome level.This study reveals the mechanism of different disease progression between LTNPs and TPs through functional enrichment analysis and differentially expressed genes(DEGs) analysis.
2021-02-10 | E-MTAB-9997 | biostudies-arrayexpress
Project description:HIV-infected slow-progressors (SP) represent a heterogeneous group of subjects who spontaneously control HIV infection without treatment for several years while showing moderate signs of disease progression. Here we determined the frequency of SP subjects who showed loss of HIV control within our Canadian Cohort of HIV+ Slow-Progressors and identified the proinflammatory cytokine IL-32 as a robust biomarker for control failure.
2015-12-31 | GSE74790 | GEO
Project description:We assessed correlates of protection from disease progression in a rare subset of HIV-infected individuals, viremic non-progressors (VNPs). These individuals have high viral load for several years, but in contrast to the majority of infected individuals, they do not progress to AIDS. Here we found this lack of progression was associated with selective preservation of two essential subsets of memory CD4+ T cells, central memory (TCM) and stem-cell memory (TSCM) cells. Compared to HIV-infected putative progressors, VNPs had higher proliferation of these indispensable subsets of memory cells, which was associated with the number of TCM. In addition, the long-lived CD4+ TCM and TSCM cells in VNPs had decreased HIV infection compared to the less critical effector memory CD4+ T cells, which indicates a possible mechanism by which VNPs maintain their CD4+ T cell pool after several years of infection, and remain free from AIDS progression. 6 HIV-infected patients fitting the clinical criteria of Viremic Non-Progressors were identified. VNPs were defined as having confirmed HIV-1 infection for at least 9 years with sustained plasma HIV RNA levels >10,000 copies/ml and maintenance of peripheral blood CD4+ T cell counts >500 cells/mm3 and a CD4% (of all lymphocytes) >15%. As controls, 7 HIV-infected Putative Progressors were identified. PPs were defined as having plasma HIV RNA levels >10,000 copies/mL, CD4+ T cell counts >400 cells/mm3 and having been initially infected with HIV 2-24 months prior to the index visit. The estimated date of initial HIV infection was calculated according to published algorithms that incorporate âde-tunedâ anti-HIV-1 antibody ELISA results or by a documented sero-conversion window of <6 months. All participants were required to be antiretroviral therapy (ART)-naïve. RNA from 6 VNP and 7 PPs was purified from PAXgene whole blood tubes and hybridized to Affymetrix U133 Plus 2.0 arrays. During data analysis, one VNP patient (PID 4015) was determined to be an outlier and removed from further analysis. Thus, 5 VNPs and 7 PPs are represented in this Series.
2016-05-15 | E-GEOD-57730 | biostudies-arrayexpress
Project description:A significant percentage of HIV-infected individuals experience a sharp decline in CD4+ T cell counts and progress to AIDS quickly after primary infection. Identification of biomarkers distinguishing rapid progressors (RPs) versus chronic progressors (CPs) is critical for early clinical intervention and could provide novel strategies to facilitate vaccine design and immune therapy. mRNA and miRNA expression profiles in the peripheral blood mononuclear cells (PBMCs) of RPs and CPs were investigated at 111±22 days (Mean±SD) of HIV infection. The association of mRNA and miRNA expression with disease progression was examined by receiver operating characteristic analysis and Kaplan-Meier survival analysis. Pathway enrichment analysis showed that genes with deregulated expression in RPs are primarily involved in apoptosis pathways. Furthermore, we found that 5 miRNAs (miR-31, -200c, -526a, -99a and -503) in RPs were significantly decreased compared to those in CPs (P<0.05). The decreased expression of these miRNAs was associated with rapid disease progression of HIV infection with a 94% predictive value as measured by the area under the curve. The upregulated predicted targets from the 5 signature miRNAs and all upregulated genes identified from mRNA microarray converged to the apoptosis pathway. Moreover, overexpression of miR-31 in primary human T cells promoted their survival. Our results have identified a distinct transcriptomic signature in PBMCs of RPs and provided novel insights to the pathogenesis of HIV infection. The initial 347 miRNA array was performed in 11 RPs, 6 CPs and 4 corresponding matched normal controls (training group); and only the miRNAs differentially expressed between RPs and CPs (P<0.05) in training group were detected in a subsequent validation group (19 RPs versus 10 CPs). miRNAs differentially expressed in 17 early HIV infected patients (including 11 RPs and 6 CPs) and 4 healthy controls in training cohort were firstly identified. Then, miRNAs differed RPs from CPs were compared in both training and validation cohort.
2013-05-01 | E-GEOD-44332 | biostudies-arrayexpress
Project description:A significant percentage of HIV-infected individuals experience a sharp decline in CD4+ T cell counts and progress to AIDS quickly after primary infection. Identification of biomarkers distinguishing rapid progressors (RPs) versus chronic progressors (CPs) is critical for early clinical intervention and could provide novel strategies to facilitate vaccine design and immune therapy. mRNA and miRNA expression profiles in the peripheral blood mononuclear cells (PBMCs) of RPs and CPs were investigated at 111±22 days (Mean±SD) of HIV infection. The association of mRNA and miRNA expression with disease progression was examined by receiver operating characteristic analysis and Kaplan-Meier survival analysis. Pathway enrichment analysis showed that genes with deregulated expression in RPs are primarily involved in apoptosis pathways. Furthermore, we found that 5 miRNAs (miR-31, -200c, -526a, -99a and -503) in RPs were significantly decreased compared to those in CPs (P<0.05). The decreased expression of these miRNAs was associated with rapid disease progression of HIV infection with a 94% predictive value as measured by the area under the curve. The upregulated predicted targets from the 5 signature miRNAs and all upregulated genes identified from mRNA microarray converged to the apoptosis pathway. Moreover, overexpression of miR-31 in primary human T cells promoted their survival. Our results have identified a distinct transcriptomic signature in PBMCs of RPs and provided novel insights to the pathogenesis of HIV infection. A cohort of primary HIV infected individuals with different disease outcome were enrolled in this study. We included 6 individuals with rapid disease progression (RP), seven with chronic disease progression (CP). The HIV infected individuals were never on therapy before the time of sample taken.
2013-05-01 | E-GEOD-44216 | biostudies-arrayexpress
Project description:From the analysis of all genes included in the array a number of individual genes were identified as dys-regulated in HIV-1 infected patients compared to healthy controls. In particular, increased CXCL13 expression in all individual patient samples. Abstract from publication: HIV-1 infection is associated with B-cell abnormalities such as hypergammaglobulinemia, poor immunisation responses and loss of serological memory. To determine whether altered expression of chemokine receptors and their ligands may play a role in B-cell dysfunctions during HIV-1 infection, the expression of CXCR4, CXCR5 and CCR7 receptors and their respective ligands on CD19+ B-cells were examined in HIV-1 infected patients and controls. We report a decreased CXCR5 expression on B-cells from patients (p<0.05), a phenomenon associated with a low CD4 T-cell count (<350 cells/µl). Interestingly, an increased expression of CXCL13, the ligand for CXCR5, was found in peripheral B-cells from HIV-1 infected patients. Moreover upon B-cell activation in vitro, CXCL13 was secreted in culture. In addition, CXCL13 positive B-cells were also found in the lymph nodes of HIV-1 infected patients, but not in control tissue. B-cell migration towards CXCL13, CXCL12 and CCL21, ligands for CXCR5, CXCR4 and CCR7, was also evaluated. In patients with a low CD4 Tcell count, migration towards all ligands was increased. Our findings indicate that altered expression of the chemokine receptor-ligand pair, CXCR5/CXCL13 may participate in the establishment of B-cell dysfunctions during HIV-1 infection.
2008-09-19 | GSE12597 | GEO
Project description:From the analysis of all genes included in the array a number of individual genes were identified as dys-regulated in HIV-1 infected patients compared to healthy controls. In particular, increased CXCL13 expression in all individual patient samples. Abstract from publication: HIV-1 infection is associated with B-cell abnormalities such as hypergammaglobulinemia, poor immunisation responses and loss of serological memory. To determine whether altered expression of chemokine receptors and their ligands may play a role in B-cell dysfunctions during HIV-1 infection, the expression of CXCR4, CXCR5 and CCR7 receptors and their respective ligands on CD19+ B-cells were examined in HIV-1 infected patients and controls. We report a decreased CXCR5 expression on B-cells from patients (p<0.05), a phenomenon associated with a low CD4 T-cell count (<350 cells/µl). Interestingly, an increased expression of CXCL13, the ligand for CXCR5, was found in peripheral B-cells from HIV-1 infected patients. Moreover upon B-cell activation in vitro, CXCL13 was secreted in culture. In addition, CXCL13 positive B-cells were also found in the lymph nodes of HIV-1 infected patients, but not in control tissue. B-cell migration towards CXCL13, CXCL12 and CCL21, ligands for CXCR5, CXCR4 and CCR7, was also evaluated. In patients with a low CD4 Tcell count, migration towards all ligands was increased. Our findings indicate that altered expression of the chemokine receptor-ligand pair, CXCR5/CXCL13 may participate in the establishment of B-cell dysfunctions during HIV-1 infection. Total RNA was extracted from purified peripheral B-cells from 4 controls and 4 patients.
2010-06-25 | E-GEOD-12597 | biostudies-arrayexpress