Unknown,Transcriptomics,Genomics,Proteomics

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T lymphocytes from Chronic HCV-infected patients express unique pro-apoptotic gene signature.

ABSTRACT: Although extensive studies have demonstrated the gene expression patterns of antigen-specific CD4+ and CD8+ T-cells during chronic hepatitis C virus (HCV) infection, the transcriptional profiles of global CD4+ and CD8+ T-cells remains unclear. In this report, we recruited 10 long-term (~20 years) treatment-naM-CM-/ve chronic HCV (CHC) patients and 5 healthy donors (HDs) to investigate differences in global CD4+ and CD8+ T-cells gene expression profile. Global CD4+ and CD8+ T-cells showed unique transcriptional profiles in the expression of apoptosis-related genes. We identified BCL2, PMAIP1, and CASP1 in CD4+ T-cells and IER3 and BCL2A1 in CD8+ T-cells from CHC patients as HCV-specific gene signatures. The unique apoptosis-related gene expression profilesin global CD4+ and CD8+ T-cells programmed by chronic HCV infection seemed to enhance activation-induced apoptosis, which was suffered by global CD4+ and CD8+ T-cells. We obtained 15 blood samples to identify the gene expression signatures of global CD4+ and CD8+ T-cells due to chronic HCV infection. The samples included: 5 samples from high HCV viral load patients (HCV-h), 5 samples from low HCV viral load (HCV-l) and 5 samples from healthy donors (HD). HCV patients were all Ab+ and treatment-naive prior to the study. Samples were taken once from each individual. Global CD4+ and CD8+ T-cells were enriched by microbeads, and total RNA were used in gene chip analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Binbin Zhao

PROVIDER: E-GEOD-49954 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Chronic immune activation is a hallmark of human immunodeficiency virus (HIV) infection and the best prognostic indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART) restores normal immune response and effectively prolongs life. In HIV-infected individuals who are coinfected with hepatitis C virus (HCV) the immune system is activated despite effective HIV antiretroviral therapy controlling viral load. Here we examined CD14+ monocyte gene expression by high-density microarray analysis and T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV, monoinfected HIV and HIV/HCV coinfected subjects with undetected HIV viral load. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological (NP) performance, which was summarized as global deficit scores (GDS). Gene expression analysis of CD14+ monocytes from coinfected subjects revealed an elevated type 1 interferon (IFN) response profile unique to coinfection. For both CD4 and CD8 T cells, coinfection triggered significantly increased expression of activation markers CD38 and HLA-DR. In the coinfected group, mild cognitive impairment was associated with a type 1 IFN monocyte response but not plasma lipopolysaccharide. These observations raise the possibility that cognitive impairment evident in the HIV/HCV population is associated with the IFN response detected in coinfected individuals. Monocytes isolated from healthy controls (n=17), HCV monoinfected (n=19) and HIV/HCV coinfected (n=17) were analyzed for gene expression using high-density microarrays. Whole blood was collected in Vacutainer CPT tubes (BD Biosciences) and PBMCs were enriched by centrifugation. Typically, three million CD14+ monocytes were isolated from 30 ml of whole blood using an anti-CD14 monoclonal antibody immunomagnetic - ferrous bead conjugate according to the manufacturer’s instructions (Miltenyi Biotech). Monocyte purity exceeded 97% with <1% T or B cell contamination as determined by flow cytometry. Monocyte RNA was isolated using a Qiagen RNeasy Micro Kit with an RNA integrity value exceeding 9. Complementary DNA was synthesized and labeled with biotin (iExpress iAmplify kit, Applied Microarrays) and hybridized to Codelink Whole Human Genome Bioarrays (55K probes, Applied Microarrays). Slides were scanned (Axon GenePix 4000B, Molecular Devices), analyzed (CodeLink Expression Software Kit v4.1) and microarray data were normalized with loess normalization using R and Bioconductor package. Determination of differential gene expression and multiple testing correction / false discovery rate adjustments were performed using GeneSpring GX 7.3 software package (Agilent). Microarray data was analyzed using a variety of custom data analytic techniques for gene expression profile identification as described previously. Correlations were determined by Spearman rank correlation coefficient.

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T lymphocytes from Chronic HCV-infected patients express unique pro-apoptotic gene signature.

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