Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA215683 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This study characterizes the effects of chronic Hepatitis C virus (HCV) infection on gene expression by analyzing blood samples from 10 treatment-naive HCV patients and 6 healthy volunteers. Differential expression analysis of microarray data from peripheral blood mononuclear cells (PBMCs) identified a 136 gene signature, including 66 genes elevated in infected individuals. Most of the up-regulated genes were associated with interferon (IFN) activity (including members of the OAS and MX families, ISG15 and IRF7), suggesting an ongoing immune response. This HCV signature was also found to be consistently enriched in many other viral infection and vaccination datasets. Validation of these genes was carried out using a second cohort composed of 5 HCV patients and 5 healthy volunteers, confirming the up-regulation of the IFN signature. In summary, this is the first study to directly compare blood transcriptional profiles from HCV patients with healthy controls. The results show that chronic HCV infection has a pronounced effect on gene expression in PBMCs of infected individuals, and significantly elevates the expression of a subset of interferon-stimulated genes.
2012-10-22 | GSE40223 | GEO
Project description:This study characterizes the effects of chronic Hepatitis C virus (HCV) infection on gene expression by analyzing blood samples from 10 treatment-naive HCV patients and 6 healthy volunteers. Differential expression analysis of microarray data from peripheral blood mononuclear cells (PBMCs) identified a 136 gene signature, including 66 genes elevated in infected individuals. Most of the up-regulated genes were associated with interferon (IFN) activity (including members of the OAS and MX families, ISG15 and IRF7), suggesting an ongoing immune response. This HCV signature was also found to be consistently enriched in many other viral infection and vaccination datasets. Validation of these genes was carried out using a second cohort composed of 5 HCV patients and 5 healthy volunteers, confirming the up-regulation of the IFN signature. In summary, this is the first study to directly compare blood transcriptional profiles from HCV patients with healthy controls. The results show that chronic HCV infection has a pronounced effect on gene expression in PBMCs of infected individuals, and significantly elevates the expression of a subset of interferon-stimulated genes.
2012-10-22 | GSE40184 | GEO
Project description:Hepatitis C virus (HCV) remains a significant public health threat as new 1.75 million HCV infections emerged worldwide. The majority of these infections become persistently infected, while around 30 % spontaneously eliminate the virus. Clinical factors for viral clarification are related to HCV interaction with host immune system, but little is known about the consequences after HCV spontaneous resolution. These individuals are difficult to recruit and study as acute infection is usually asymptomatic, and they will not be identified unless it progress to chronic infection. The study of peripheral blood mononuclear cells (PBMCs) of these patients is crucial, as PBMCs are one of the main HCV extrahepatic reservoirs, and its transcriptional profile provide us information of innate and adaptive immune response against HCV infection. Our research shows novel insight on molecular consequences of spontaneous resolution after an acute HCV infection. 96 Individuals with different HCV exposure status were recruited: spontaneous resolved, chronic infected and healthy controls; and the microRNA profile of their PBMCs were analyzed. Our results indicate similar disruption of miRNA expression on HCV chronic patients and those who spontaneously clarified the infection, compared to control patients. The disrupted miRNAs formed a signature of 21 miRNAs that mainly regulate lipid metabolism. This is the first report showing miRNA profile similarities between chronic HCV patients and spontaneous resolved individuals. Thus, our results suggest that HCV infection promotes molecular alterations in PBMCs that will last longer after HCV spontaneous eradication. This evidences open up new prospects in the management of individuals who spontaneously clarified infection, as they should be monitored and followed to dismiss future HCV-related complications, such us liver diseases complications. The identified miRNA signature could be used as biomarker to monitor HCV fingerprint on HCV-exposed patients.
2019-06-21 | E-MTAB-8023 | biostudies-arrayexpress
Project description:Hepatitis C Virus is a leading cause of chronic liver disease. The identification and characterisation of key host cellular factors that play a role in the HCV replication cycle is important for the understanding of disease pathogenesis and the identification of novel anti-viral therapeutic targets. Gene expression profiling of HCV infected Huh7 cells by microarray analysis was performed to identify host cellular genes that are transcriptionally regulated by infection. The expression of host genes involved in cellular defence mechanisms (apoptosis, proliferation and anti-oxidant responses), cellular metabolism (lipid and protein metabolism) and intracellular transport (vesicle trafficking and cytoskeleton regulation) was significantly altered by HCV infection. The gene expression patterns identified provide insight into the potential mechanisms that contribute to HCV associated pathogenesis. These include an increase in pro-inflammatory and pro-apoptotic signalling and a decrease in the anti-oxidant response pathways of the infected cell.
2010-05-01 | GSE20948 | GEO
Project description:This study characterizes the effects of chronic Hepatitis C virus (HCV) infection on gene expression by analyzing blood samples from 10 treatment-naive HCV patients and 6 healthy volunteers. Differential expression analysis of microarray data from peripheral blood mononuclear cells (PBMCs) identified a 136 gene signature, including 66 genes elevated in infected individuals. Most of the up-regulated genes were associated with interferon (IFN) activity (including members of the OAS and MX families, ISG15 and IRF7), suggesting an ongoing immune response. This HCV signature was also found to be consistently enriched in many other viral infection and vaccination datasets. Validation of these genes was carried out using a second cohort composed of 5 HCV patients and 5 healthy volunteers, confirming the up-regulation of the IFN signature. In summary, this is the first study to directly compare blood transcriptional profiles from HCV patients with healthy controls. The results show that chronic HCV infection has a pronounced effect on gene expression in PBMCs of infected individuals, and significantly elevates the expression of a subset of interferon-stimulated genes. Whole blood was collected from a group of 10 patients who were infected with genotype 1 hepatitis C, before initiation of treatment at the Indiana University School of Medicine. Control blood samples were harvested from healthy student volunteers. Peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood samples of the cohort using centrifugation through a 10-ml Ficoll-Hypaque gradient (Amersham/Pharmacia, Piscataway, NJ), and RNA was isolated within a few hours. RNA was then processed according to the protocols recommended by Affymetrix (Santa Clara, CA), and run on an Affymextrix Human Genome U133 array.
2012-10-22 | E-GEOD-40184 | biostudies-arrayexpress
Project description:Although treatment of chronic hepatitis C virus (HCV) infection with direct acting antivirals (DAAs) results in high rates of cure, liver fibrosis does not resolve immediately after HCV eradication. Resolution of fibrosis occurs in some, but not all patients, after HCV cure, and hepatic decompensation and hepatocellular carcinoma can still occur in patients with pre-existing cirrhosis. We hypothesized that evaluation of the host liver proteome in the context of HCV treatment would provide insight into how inflammatory and fibrinogenic pathways change upon HCV eradication. We evaluated the whole liver proteome and phosphoproteome using paired liver biopsies from 8 HCV-infected patients collected before or immediately after treatment with DAAs in clinical trials. We identify interferon stimulated proteins as the predominant pathways that decrease with HCV treatment, which is consistent with previous analyses of the liver transcriptome during DAA therapy. While there was no change in the proteome of pathways associated with liver fibrosis, we identified a decrease in the phosphoproteome signature for ERK1/ERK2 as a result of HCV treatment. Conclusion: There is a reduction in the endogenous interferon-mediated antiviral response and alterations in the phosphoproteome that may precede resolution of fibrosis in the liver immediately after treatment of HCV with DAAs.
2023-03-11 | PXD024846 | Pride
Project description:This study characterizes the effects of chronic Hepatitis C virus (HCV) infection on gene expression by analyzing blood samples from 10 treatment-naive HCV patients and 6 healthy volunteers. Differential expression analysis of microarray data from peripheral blood mononuclear cells (PBMCs) identified a 136 gene signature, including 66 genes elevated in infected individuals. Most of the up-regulated genes were associated with interferon (IFN) activity (including members of the OAS and MX families, ISG15 and IRF7), suggesting an ongoing immune response. This HCV signature was also found to be consistently enriched in many other viral infection and vaccination datasets. Validation of these genes was carried out using a second cohort composed of 5 HCV patients and 5 healthy volunteers, confirming the up-regulation of the IFN signature. In summary, this is the first study to directly compare blood transcriptional profiles from HCV patients with healthy controls. The results show that chronic HCV infection has a pronounced effect on gene expression in PBMCs of infected individuals, and significantly elevates the expression of a subset of interferon-stimulated genes. Treatment-naM-CM-/ve HCV patients were recruited by hepatologists in the outpatient hepatitis clinic within the Yale Liver Center. Healthy volunteers were recruited from YaleM-bM-^@M-^Ys PhenoGenetic Cohort of Healthy controls. PBMCs were isolated from whole blood by density gradient centrifugation using Ficoll-Paque (GE Healthcare) centrifugation. Total RNA was isolated from PBMCs using an RNeasy kit (Qiagen, Valencia, CA), and the quality of total RNA was evaluated by A260/A280 ratio and by electrophoresis on an Agilent Bioanalyzer. All subsequent processing, hybridization to the Illumina HumanHT-12 microarray, and quality control analyses were carried out by the Yale Center for Genome Analysis using standard protocols.
2012-10-22 | E-GEOD-40223 | biostudies-arrayexpress
Project description:Purpose: This study unravel the mechanisms that link viral infection and cancer Methods:Human HCC cell line and HCC liver FFPE samples from HCC patients from three etiology groups- HBV, HCV infection, or neither were taken to explore their genomic DNA in two aspects: The HCC genomic mutations within the exons of 224 candidate genes, frequently mutated in HCC, using SureSelect™ Target Enrichment System kit and the transient response of liver cells to HCV infection, in genome wide histone modifications and gene expression, as demonstrated by ChIP-Seq and RNA-Seq. Results:Mutational signature was explored by high-resolution targeted sequencing that detected low-frequency passenger mutations in 64 HCC samples from three etiology groups – HBV, HCV, or other. We identified novel distinct etiology-dependent regional mutations signatures. To explore the link between genomic signature and genome wide chromatin organization we studied the epigenetic changes occur following HCV infection. We demonstrated that HCV infection induces epigenetic changes that persist as "epigenetic signature" following virus eradication and reprogram host gene expression. High mutation rate associated with HCV etiology correlated with HCV-induced changes in epigenetic markers leading to closed chromatin. Conclusions:We present a new link between cancer causing mutagenesis, and increase in liver cancer predisposition in chronic HCV-infected individuals. The sequential events begin with HCV-specific epigenetic signature that in turn dictates a unique HCV-specific somatic mutational profile in HCC
2018-09-12 | GSE103729 | GEO
Project description:Purpose: This study unravel the mechanisms that link viral infection and cancer Methods:Human HCC cell line and HCC liver FFPE samples from HCC patients from three etiology groups- HBV, HCV infection, or neither were taken to explore their genomic DNA in two aspects: The HCC genomic mutations within the exons of 224 candidate genes, frequently mutated in HCC, using SureSelect™ Target Enrichment System kit and the transient response of liver cells to HCV infection, in genome wide histone modifications and gene expression, as demonstrated by ChIP-Seq and RNA-Seq. Results:Mutational signature was explored by high-resolution targeted sequencing that detected low-frequency passenger mutations in 64 HCC samples from three etiology groups – HBV, HCV, or other. We identified novel distinct etiology-dependent regional mutations signatures. To explore the link between genomic signature and genome wide chromatin organization we studied the epigenetic changes occur following HCV infection. We demonstrated that HCV infection induces epigenetic changes that persist as "epigenetic signature" following virus eradication and reprogram host gene expression. High mutation rate associated with HCV etiology correlated with HCV-induced changes in epigenetic markers leading to closed chromatin. Conclusions:We present a new link between cancer causing mutagenesis, and increase in liver cancer predisposition in chronic HCV-infected individuals. The sequential events begin with HCV-specific epigenetic signature that in turn dictates a unique HCV-specific somatic mutational profile in HCC
2018-09-12 | GSE103728 | GEO
Project description:Hepatitis C Virus is a leading cause of chronic liver disease. The identification and characterisation of key host cellular factors that play a role in the HCV replication cycle is important for the understanding of disease pathogenesis and the identification of novel anti-viral therapeutic targets. Gene expression profiling of HCV infected Huh7 cells by microarray analysis was performed to identify host cellular genes that are transcriptionally regulated by infection. The expression of host genes involved in cellular defence mechanisms (apoptosis, proliferation and anti-oxidant responses), cellular metabolism (lipid and protein metabolism) and intracellular transport (vesicle trafficking and cytoskeleton regulation) was significantly altered by HCV infection. The gene expression patterns identified provide insight into the potential mechanisms that contribute to HCV associated pathogenesis. These include an increase in pro-inflammatory and pro-apoptotic signalling and a decrease in the anti-oxidant response pathways of the infected cell. 5x105 Huh7 cells were seeded in 25cm2 culture flasks and infected in triplicate either with the genotype 2a HCV clone, JFH-1 at a multiplicity of infection (MOI) of 3 or mock infected with an equal volume of concentrated conditioned growth medium. At 6, 12, 18, 24 and 48 hours post-infection, cellular RNA was extracted using TRIzol reagent (Invitrogen). Trizol lysates were shipped to Expression Analysis (NC, USA) where RNA was purified, quality tested using the Agilent Bioanalyser and hybridised onto Human U133 Plus 2.0 Affymetrix microarray chips for fluorescence data acquisition. In summary, a total of 30 RNA samples were analysed including 3x mock infected samples taken at 6, 12, 18, 24 and 48 hours post-treatment and 3x JFH-1 infected samples taken at 6, 12, 18, 24 and 48 hours post-infection. Two samples (Mock_6hrs_1 and JFH-1_6hrs_1) did not pass our data quality control measures and were therefore excluded from the statistical analysis.
2010-05-27 | E-GEOD-20948 | biostudies-arrayexpress