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.
Project description:Human gut is the primary site for HIV-1 infection. However, most of transcriptomic studies so far were based on peripheral blood (PBMC). The current study compared the transcriptomes of human LPMC between healthy controls and chronically HIV-1 infected patients.
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. 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.
Project description:Sexually transmitted infections (STIs) are commonly reported among HIV-1 infected patients. The increasing prevalence of the most common STI, Chlamydia trachomatis (CT), among HIV-1 infected people suggests a role in HIV-1 infectivity. However, the mechanisms modulating the enhancement of HIV-1 infectivity during HIV-1/STIs coinfection remain elusive. The stimulation of CD4 T cells during CT infection may modulate the expression of specific genes, which in turn enhance the susceptibility and infectivity of CT-specific CD4 T cells to HIV-1 infection. After three days of CT stimulation of PBMCs followed by 3 days of HIV-1 infection, we observed a significant increase in HIV-1 p24 levels among clinically diagnosed C. trachomatis-infected patients as compared to cells from healthy donors. Similarly, ex vivo CT antigen-stimulated PBMCs from healthy donors showed enhanced susceptibility to HIV-1 as compared to unstimulated PBMCs. CT-specific CD4 T cells also harbour more HIV-1 copy numbers as compared to healthy unstimulated CD4 T cells. RNA-seq data revealed the upregulation of CCR chemokine receptors and cytokines in CD4 T cells from CT-stimulated CD4 T cells infected with HIV-1.
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.
Project description:CD4+ T-cells are the main target of HIV-1 and several host factors can positively or negatively modulate HIV-1 infection of these cells. MiRNAs aresmall regulatory RNAs that are involved in the regulation of basic cellular functions. They are also increasingly recognized as host factors regulatingHIV-1 infection, replication and persistence. In order to identify miRNAs involved in HIV-1 infection of CD4+ T-cells, we performed globaltranscriptomic analyses of productively infected and HIV-1 exposed but non infected bystander CD4+ T-cells and compared their MIRNA profiles with uninfected cells. Theseanalyses were performed in CD4+T-cells isolated from 3 different healthy blood donors. Both miRNA and mRNA expression profiles were compared. Our results show that bystander and uninfected CD4+ T-cells do not display important differences in their miRNA expression profiles even though their respectivemRNA expression profiles were markedly different. In contrast, both mRNA and miRNA expressionprofiles from productively infected CD4+ T-cells were significantly different from those of uninfected cells. Overall, these results suggest that HIV-1infection impacts the miRNA expression profile of primary CD4+ T-cells.
Project description:CD4+ T-cells are the main target of HIV-1 and several host factors can positively or negatively modulate HIV-1 infection of these cells. MiRNAs aresmall regulatory RNAs that are involved in the regulation of basic cellular functions. They are also increasingly recognized as host factors regulatingHIV-1 infection, replication and persistence. In order to identify miRNAs involved in HIV-1 infection of CD4+ T-cells, we performed globaltranscriptomic analyses of productively infected and HIV-1 exposed but non infected bystander CD4+ T-cells and compared their MIRNA profiles with uninfected cells. Theseanalyses were performed in CD4+T-cells isolated from 3 different healthy blood donors. Both miRNA and mRNA expression profiles were compared. Our results show that bystander and uninfected CD4+ T-cells do not display important differences in their miRNA expression profiles even though their respectivemRNA expression profiles were markedly different. In contrast, both mRNA and miRNA expressionprofiles from productively infected CD4+ T-cells were significantly different from those of uninfected cells. Overall, these results suggest that HIV-1infection impacts the miRNA expression profile of primary CD4+ T-cells.
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.
Project description:PolyA-RNA sequencing on Peripheral Blood Mononuclear Cells in patients infected with HIV and healthy donnors. Patients were effectively treated with cART (virological controlled and CD4+ T-cell counts over 500) for an extended period. HIV infected patients were not coinfected with HCV or HBV.
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.