Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-seq to investigate gene expression after HCV eradication with IFN therapy in HIV/HCV-coinfected patients

ABSTRACT: We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after the sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-group) were included as a control group, which were effectively treated with cART (virological controlled and CD4+ T-cell counts over 500) for an extended period. RNA-seq analysis was performed on peripheral blood mononuclear cells (PBMCs).

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Homo sapiens

SUBMITTER: Salvador Resino Garcia

PROVIDER: E-MTAB-10232 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients.

Brochado Óscar Ó Martínez Isidoro I Berenguer Juan J Medrano Luz L González-García Juan J Jiménez-Sousa María Ángeles MÁ Carrero Ana A Hontañón Víctor V Navarro Jordi J Guardiola Josep M JM Fernández-Rodríguez Amanda A Resino Salvador S

Journal of biomedical science 20210330 1

<h4>Objective</h4>To evaluate the impact of hepatitis C virus (HCV) elimination via interferon (IFN)-based therapy on gene expression profiles related to the immune system in HIV/HCV-coinfected patients.<h4>Methods</h4>We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-mono) were included as a control. RNA-seq analysis was p ...[more]

PMID: 33785040

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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.

Dataset Information

RNA-seq to investigate gene expression after HCV eradication with IFN therapy in HIV/HCV-coinfected patients

Publications

HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients.

Similar Datasets

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