Circadian control of hepatitis B virus replication
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ABSTRACT:
PROVIDER: PRJNA685550 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The natural history of chronic hepatitis B virus (HBV) infection could be divided in different phases by transaminase and HBV replication levels. However, it remains unknown how the intrahepatic transcriptomes in patients are correlated with the clinical phases. Here, we determined the intrahepatic transcriptomes of chronic hepatitis B patients and examined the role of specific groups of genes, including immune-related genes, in the control of hepatitis B virus infection.
2016-03-31 | GSE65359 | GEO
Project description:The natural history of chronic hepatitis B virus (HBV) infection could be divided in different phases by transaminase and HBV replication levels. However, it remains unknown how the intrahepatic transcriptomes in patients are correlated with the clinical phases. Here, we determined the intrahepatic transcriptomes of chronic hepatitis B patients and examined the role of specific groups of genes, including immune-related genes, in the control of hepatitis B virus infection. The transcriptomes of 83 chronic hepatitis B patients (22 immune tolerant, 50 immune clearance, and 11 inactive carrier state) were analyzed by performing microarray analysis of liver biopsies.KEGG pathway analysis showed that immune response genes and interferon-stimulated genes were up-regulated in the immune clearance phase. Although immune tolerant patients and inactive state carriers had significantly different serum viral loads, the hepatic transcriptomes of the two groups were largely similar and only significantly differed in the expression of 109 genes (p < 0.01). Thus, we hypothesized that some of the 109 genes may be involved in HBV control and identified genes of interest by performing systematic screening using specific siRNAs. We showed that silencing candidate genes such as EVA1A resulted in significantly increased viral replication. Conversely, overexpression of candidate genes suppressed virus replication. Conclusions: The immune related pathways were up-regulated in the immune clearance phase but not in the inactive carrier phase. A number of host genes unrelated to immune pathways were expressed in the inactive carrier phase and these may participate in the control of hepatitis B virus replication, resulting in low viral replication. This dataset is part of the TransQST collection.
2016-03-31 | E-GEOD-65359 | biostudies-arrayexpress
Project description:Gene expression profiling was carried out in Huh-7.5 cells in which miR-27a was over- or under-expressed. Transfection of cells with pre-miR-27a and pre-miR-control, or anti-miR-27a and anti-miR-control enabled down- and up-regulated genes to be determined, respectively. Replication and infectivity of the lipotrophic hepatitis C virus (HCV) is regulated by cellular lipid status. Among differentially expressed micro (mi)RNAs, we found that miR-27a was preferentially expressed in HCV-infected compared with hepatitis B virus (HBV)-infected liver. Gene expression profiling of Huh-7.5 cells showed that miR-27a regulates lipid metabolism by targeting the lipid synthetic transcriptional factor, RXRα, and the lipid transporter, ABCA1
2013-06-05 | GSE41737 | GEO
Project description:Hepatitis Delta virus (HDV) is a satellite of Hepatitis B virus with a single stranded circular RNA genome. HDV RNA genome synthesis is carried out in infected cells by cellular RNA polymerases with the assistance of the small hepatitis delta antigen (S-HDAg). Here we show that S-HDAg binds the Bromodomain (BRD) Adjacent To Zinc Finger Domain 2B (BAZ2B) protein, a regulatory subunit of BRF (BAZ2B-Associated Remodeling Factor) ISWI chromatin remodeling complexes. ShRNAs-mediated silencing of BAZ2B or its inactivation with the BAZ2B-BRD inhibitor GSK-2801 impairs HDV replication in HDV-infected human hepatocytes. S-HDAg contains a short linear interacting motif (SLiM) KacXXR, similar to the one recognized by BAZ2B-BRD in histone H3. We found that the integrity of the S-HDAg SLiM sequence is required for S-HDAg interaction with BAZ2B-BRD and for HDV RNA replication. Our results suggest that S-HDAg uses a histone mimicry strategy to co-activate the RNA Polymerase II-dependent synthesis of HDV RNA and sustain HDV replication.
2020-05-27 | PXD016880 | Pride
Project description:Background: Hepatitis C virus (HCV) infects human liver hepatocytes, often leading to liver cirrhosis and hepatocellular carcinoma (HCC). It is believed that chronic infection alters host gene expression and favours HCC development. In particular, HCV replication in Endoplasmic Reticulum (ER) derived membranes induces chronic ER stress. How HCV replication affects host mRNA translation and transcription at a genome wide level is not yet known. Methods: We used Riboseq (Ribosome Profiling) to analyze transcriptome and translatome changes in Huh-7.5 hepatoma cells replicating HCV for 6 days. Results: Established viral replication does not cause global changes in host gene expression - only around 30 genes are differentially expressed. Upregulated genes are related to ER stress, HCV replication and HCC development. Some mRNAs (PPP1R15A/GADD34, DDIT3/CHOP, TRIB3) may be subject to uORF mediated translation control in response to stress-induced eIF2 inactivation. Transcriptional downregulation mainly affects mitochondrial respiratory chain complex genes. Conclusion: After establishing HCV replication, cellular gene expression is reprogrammed towards stress response and HCC development. Downregulation of mitochondrial respiratory chain genes indicates how a virus induces cancer cell-like metabolic reprogramming ("Warburg effect"). Thus, HCV escapes stress response pathways but induces selective gene expression changes which likely are beneficial for chronic infection and cancerogenesis.
2019-03-02 | GSE127713 | GEO
Project description:Gene expression profiling was carried out in Huh-7.5 cells in which miR-27a was over- or under-expressed. Transfection of cells with pre-miR-27a and pre-miR-control, or anti-miR-27a and anti-miR-control enabled down- and up-regulated genes to be determined, respectively. Replication and infectivity of the lipotrophic hepatitis C virus (HCV) is regulated by cellular lipid status. Among differentially expressed micro (mi)RNAs, we found that miR-27a was preferentially expressed in HCV-infected compared with hepatitis B virus (HBV)-infected liver. Gene expression profiling of Huh-7.5 cells showed that miR-27a regulates lipid metabolism by targeting the lipid synthetic transcriptional factor, RXRα, and the lipid transporter, ABCA1 Carrying out a Target Scan (Release 5.2) of miR-27a predicted 921 candidate target genes, and functional gene ontology enrichment analysis of these genes by MetaCore (Thomson Reuters, NY) showed that miR-27a could target the signaling pathways of cytoskeleton remodeling and lipid metabolism . To examine whether these signaling pathways were regulated by miR-27a, gene expression profiling was carried out in Huh-7.5 cells in which miR-27a was over- or under-expressed. Transfection of cells with pre-miR-27a and pre-miR-control, or anti-miR-27a and anti-miR-control enabled down- and up-regulated genes to be determined, respectively. Huh-7.5 cells with miR-27a over- or under-expressed
2013-06-05 | E-GEOD-41737 | biostudies-arrayexpress
Project description:Chronic liver disease and cancer are global health challenges. The role of the circadian clock (CC) as a regulator of physiology and disease is well established in animal models. However, in human liver the identity of circadian genes and their epigenetic regulation is unknown. Here, we unraveled the circadian transcriptome and epigenome of human hepatocytes using a human liver chimeric mouse model. We identified genes coding for transcription factors, chromatin modifiers, and critical enzymes which are expressed rhythmically in human hepatocytes, and which differ from the mouse liver circadian transcriptome. Moreover, we show that hepatitis C virus (HCV) infection, a major cause of liver disease and cancer world-wide, perturbs the human hepatocellular clock leading to an activation of pathways mediating steatosis, fibrosis and cancer. The HCV-disrupted rhythmic hepatic pathways remained deregulated in patients cured of HCV suggesting a major role in liver cancer development, and in the identification of therapeutic targets.
2024-08-02 | GSE200810 | GEO
Project description:Effect of mouse hepatitis virus strain A59 replication on gene expression and mRNA stability in LR cells
2007-11-13 | E-MEXP-895 | biostudies-arrayexpress
Project description:Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide for which there are no curative therapies. The major challenge in curing infection is eradicating or silencing the covalent closed circular DNA (cccDNA) form of the viral genome. The circadian factors BMAL1/CLOCK and REV-ERB are master regulators of the liver transcriptome and yet their role in HBV replication is unknown. We establish a circadian cycling liver cell-model and demonstrate that REV-ERB directly regulates NTCP-dependent hepatitis B and delta virus particle entry. Importantly, we show that pharmacological activation of REV-ERB inhibits HBV infection in vitro and in human liver chimeric mice. We uncover a role for BMAL1 to bind HBV genomes and increase viral promoter activity. Pharmacological inhibition of BMAL1 through REV-ERB ligands reduces pre-genomic RNA and de novo particle secretion. The presence of conserved E-box motifs among members of the Hepadnaviridae family highlight an evolutionarily conserved role for BMAL1 in regulating this family of small DNA viruses.
| S-EPMC7955118 | biostudies-literature