Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA345616 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Viruses lack the basic machinery needed to replicate and therefore must hijack host metabolism to propagate. Virus-induced metabolic alterations have yet to be systematically studied in the context of the host transcriptional regulation, offering insight into host-pathogen metabolic interplay. In this work we identified Hepatitis C Virus (HCV)-responsive regulators by coupling system-wide metabolic flux analysis with targeted perturbation of nuclear receptors in primary human hepatocytes. We find HCV-induced up-regulation of glycolysis, ketogenesis and drug metabolism, controlled by activation of HNF4α, PPARα, FXR and PXR, respectively. Pharmaceutical inhibition of HNF4α reversed HCV-induced glycolysis, blocking viral replication while increasing apoptosis in infected cells showing a viral-induced dependence on glycolysis. In contrast, pharmaceutical inhibition of PPARα or FXR reversed HCV-induced ketogenesis, but increased viral replication demonstrating a unique host anti-viral response. Our results show that viral-induced changes to host metabolism can be detrimental to its lifecycle demonstrating a distinct biological complexity. In this dataset, we include the expression data obtained from primary human hepatocyte oxygenated co-cultures infected or not infected by HCV and human sanp frozen liver biopsys from HCV patients at earley stages.
2016-10-07 | GSE84587 | GEO
Project description:The aim of this study was to identify differential gene and protein expression associated with GBV-C that may be of importance in reduction of HCV-related liver disease. GB virus C (GBV-C) infection leads to improved outcomes in human immunodeficiency virus (HIV) infection. Furthermore, GBV-C has been shown to reduce hepatitis C virus (HCV)-related liver disease in HCV/HIV co-infection. We aimed to identify differential gene expression associated with GBV-C in HCV/HIV co-infection by comparing RNA expression from liver biopsies of HCV/HIV co-infected patients with and without GBV-C infection. Liver biopsies were obtained from 10 Patients with HCV/HIV co-infection; 4 of these patients were positive for GBV-C infection and 6 were negative for GBV-C infection. The tissue was stored in RNAlater and RNA was extracted for hybridisation to Affymetrix Human Genome U133 plus 2.0 microarrays at the University of Texas Medical Branch Molecular Genomics Core Laboratory. The data was analysed for genes differentially expressed between GBV-C positive and negative patients using Partek Genomics suite and applying a custom CDF file (Hs133P_Hs_UG_8), available from Molecular and Behavioural Neuroscience Institute, University of Michigan.
2011-05-10 | E-GEOD-16593 | biostudies-arrayexpress
Project description:Hepatitis C virus (HCV)-induced chronic liver disease is one of the leading causes of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HCC development following chronic HCV infection remain poorly understood. MicroRNAs (miRNAs) play an important role in cellular homeostasis within the liver and deregulation of the miRNome has been associated with liver disease including HCC. While host miRNAs are essential for HCV replication, viral infection in turn appears to induce alterations of intrahepatic miRNA networks. Although the cross-talk between HCV and liver cell miRNAs most likely contributes to liver disease pathogenesis, the functional involvement of miRNAs in HCV-driven hepatocyte injury and HCC remains elusive. Here, we combined a hepatocyte-like based model system, high-throughput small RNA-sequencing, computational analysis and functional studies to investigate HCV-miRNA interactions that may contribute to liver disease and HCC. Profiling analyses indicated that HCV infection differentially regulated the expression of 72 miRNAs by at least two-fold including miRNAs that were previously described to target genes associated with inflammation, fibrosis and cancer development. Further investigation demonstrated that miR-146a-5p was consistently increased in HCV-infected hepatocyte-like cells and primary human hepatocytes as well as in liver tissues from HCV-infected patients. Genome-wide microarray and computational analyses indicated that miR-146a-5p over-expression is related to liver disease and HCC development. Furthermore, we showed that miR-146a-5p positively impacts on late steps of the viral replication cycle thereby increasing HCV infection. Collectively, our data indicate that the HCV-induced increase in miR-146a-5p expression both promotes viral infection and is relevant for pathogenesis of liver disease. To explore the functional relevance of miR-146a-5p up-regulation, we performed a genome-wide transcriptomic analysis of hepatocyte-like cells upon ectopic miR-146a-5p expression.
2016-05-09 | GSE79340 | GEO
Project description:Hepatitis C virus (HCV)-induced chronic liver disease is one of the leading causes of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HCC development following chronic HCV infection remain poorly understood. MicroRNAs (miRNAs) play an important role in cellular homeostasis within the liver and deregulation of the miRNome has been associated with liver disease including HCC. While host miRNAs are essential for HCV replication, viral infection in turn appears to induce alterations of intrahepatic miRNA networks. Although the cross-talk between HCV and liver cell miRNAs most likely contributes to liver disease pathogenesis, the functional involvement of miRNAs in HCV-driven hepatocyte injury and HCC remains elusive. Here, we combined a hepatocyte-like based model system, high-throughput small RNA-sequencing, computational analysis and functional studies to investigate HCV-miRNA interactions that may contribute to liver disease and HCC. Profiling analyses indicated that HCV infection differentially regulated the expression of 72 miRNAs by at least two-fold including miRNAs that were previously described to target genes associated with inflammation, fibrosis and cancer development. Further investigation demonstrated that miR-146a-5p was consistently increased in HCV-infected hepatocyte-like cells and primary human hepatocytes as well as in liver tissues from HCV-infected patients. Genome-wide microarray and computational analyses indicated that miR-146a-5p over-expression is related to liver disease and HCC development. Furthermore, we showed that miR-146a-5p positively impacts on late steps of the viral replication cycle thereby increasing HCV infection. Collectively, our data indicate that the HCV-induced increase in miR-146a-5p expression both promotes viral infection and is relevant for pathogenesis of liver disease.
2016-05-09 | GSE74014 | GEO
Project description:Deeper understanding of liver pathophysiology would benefit from a comprehensive quantitative proteome resource at cell-type resolution. Here, we quantify more than 10,000 proteins and 150,000 sequence-unique peptides across total liver, the major liver cell types, time-course of primary cell cultures and liver disease states. Bioinformatic analysis reveals that half of hepatocyte protein mass is comprised of enzymes and 23% of mitochondrial proteins, twice the proportion of other liver cell types. Using primary cell cultures, we capture dynamic proteome remodeling from tissue states to cell line states, providing useful information for biological or pharmaceutical research. Our extensive data serves as spectral library to characterize a human cohort of non-alcoholic steatohepatitis and cirrhosis. Dramatic proteome changes in liver biopsies include signatures of stellate cell activation resembling liver cirrhosis, providing functional insights.
2022-05-08 | PXD027722 | Pride
Project description:Hepatic complications of HCV infection, including fibrosis and cirrhosis are accelerated in HIV-infected individuals. Although liver biopsy remains the gold standard for staging HCV-associated liver disease, this test can result in serious complications and is subject to sampling error. These challenges have prompted a search for non-invasive methods for liver fibrosis staging. To this end, we compared serum proteome profiles at different stages of fibrosis in HIV/HCV co- and HCV mono-infected patients using SELDI-TOF MS.
2018-04-09 | PXD009007 | Pride
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:Virus species- and tissue-tropism is governed by host dependency and restriction factors. Hepatitis C virus (HCV) exhibits a narrow species-tropism and murine hepatocytes are refractory to infection. Using murine liver cDNA library screening we identified Cd302, a lectin, and Cr1l, a complement receptor, as pan-genotypic restrictors of HCV infection. Cd302/Cr1l interact to impede virion uptake and co-operatively induce a non-canonical transcriptional program, inhibiting HCV and hepatitis B virus (HBV) infection in vitro. CAS9 disruption of murine hepatocyte Cd302 expression increased HCV permissiveness in-vivo and ex-vivo, and modulated the intrinsic hepatocyte transcriptome dysregulating metabolic process and host defense genes. In contrast, co-operative CD302/CR1L expression was absent and HCV restriction reduced in human hepatocytes. The Cd302/Cr1l axis therefore contributes to limiting hepatotropic virus cross-species transmission to mice, opening new avenues for step-wise development of mouse models for these important human pathogens, which cause substantial disease burden globally.
2020-12-01 | GSE140578 | GEO
Project description:Virus species- and tissue-tropism is governed by host dependency and restriction factors. Hepatitis C virus (HCV) exhibits a narrow species-tropism and murine hepatocytes are refractory to infection. Using murine liver cDNA library screening we identified Cd302, a lectin, and Cr1l, a complement receptor, as pan-genotypic restrictors of HCV infection. Cd302/Cr1l interact to impede virion uptake and co-operatively induce a non-canonical transcriptional program, inhibiting HCV and hepatitis B virus (HBV) infection in vitro. CAS9 disruption of murine hepatocyte Cd302 expression increased HCV permissiveness in-vivo and ex-vivo, and modulated the intrinsic hepatocyte transcriptome dysregulating metabolic process and host defense genes. In contrast, co-operative CD302/CR1L expression was absent and HCV restriction reduced in human hepatocytes. The Cd302/Cr1l axis therefore contributes to limiting hepatotropic virus cross-species transmission to mice, opening new avenues for step-wise development of mouse models for these important human pathogens, which cause substantial disease burden globally.
2020-12-01 | GSE140577 | GEO
Project description:Virus species- and tissue-tropism is governed by host dependency and restriction factors. Hepatitis C virus (HCV) exhibits a narrow species-tropism and murine hepatocytes are refractory to infection. Using murine liver cDNA library screening we identified Cd302, a lectin, and Cr1l, a complement receptor, as pan-genotypic restrictors of HCV infection. Cd302/Cr1l interact to impede virion uptake and co-operatively induce a non-canonical transcriptional program, inhibiting HCV and hepatitis B virus (HBV) infection in vitro. CAS9 disruption of murine hepatocyte Cd302 expression increased HCV permissiveness in-vivo and ex-vivo, and modulated the intrinsic hepatocyte transcriptome dysregulating metabolic process and host defense genes. In contrast, co-operative CD302/CR1L expression was absent and HCV restriction reduced in human hepatocytes. The Cd302/Cr1l axis therefore contributes to limiting hepatotropic virus cross-species transmission to mice, opening new avenues for step-wise development of mouse models for these important human pathogens, which cause substantial disease burden globally.
2020-12-01 | GSE140590 | GEO