Hepatitis B virus protein X promotes survival and loss of hepatocyte identity in a differentiated human liver organoid system. [ATAC-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE332971 | GEO | 2026/09/01
REPOSITORIES: GEO
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Project description:In this study, we leverage liver organoids derived from adult human livers to investigate HBx function in hepatocytes. Our findings demonstrate that HBx reshapes hepatocyte identity and apoptotic signaling to promote cell survival, establishing a relevant platform to study HBV persistence and liver tumorigenesis.
2026-09-01 | GSE332970 | GEO
Project description:Hepatitis B virus (HBV) infection could cause hepatitis, liver cirrhosis and hepatocellular carcinoma. HBV-mediated pathogenesis is only partially understood, but X protein (HBx) reportedly possesses oncogenic potential. Exosomes are small membrane vesicles with diverse functions released by various cells including hepatocytes, and HBV harnesses cellular exosome biogenesis and export machineries for virion morphogenesis and secretion. Therefore, HBV infection might cause changes in exosome contents with functional implications for both virus and host. In this project, exosome protein content changes induced by HBV and HBx were quantitatively analyzed by SILAC/LC-MS/MS. Exosomes prepared from SILAC-labeled hepatoma cell line Huh-7 transfected with HBx, wildtype or HBx-null HBV replicon plasmids were analyzed by LC-MS/MS.
2014-10-09 | PXD001339 | Pride
Project description:Chronic hepatitis B virus (HBV) remains to be the most common risk factor of hepatocellular carcinoma (HCC). While previous work has primarily focussed on understanding the direct and indirect mechanisms of Hepatitis B virus X protein (HBx)-mediated hepatocarcinogenesis, from genetic and epigenetic perspectives, its influence on RNA modification mediated onset of liver malignancies is less well understood. This study explored the role of HBV-encoded HBx in altering the m6A methylome profile and its implications on the pathogenesis of HCC. We established HBx-expressing stable HCC cell lines, Huh7-HBx and HepG2-HBx, and explored the transcriptomic and epitranscriptomic profiles by RNA-seq and MeRIP-seq, respectively. Preliminary results suggest that HBx promotes liver cell proliferation, migration, survival and overall m6A methylation in HCC cells and is involved in modulating the extracellular matrix. We show that HBx mediates liver cell transformation by upregulating KIAA1429 methyltransferase. HBx also drives the expression and hypermethylation of the extracellular matrix protein HSPG2/Perlecan and promotes tumourigenesis. Furthermore, we observed a potential interaction between KIAA1429 and HSPG2 in HCC liver cancer cells and demands further investigation.
2023-08-09 | GSE240451 | GEO
Project description:Chronic hepatitis B virus (HBV) infection is an incurable global health threat capable of causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent chromosome, cccDNA, consisting of the circular viral genome and host histones. The first viral protein expressed, HBx, induces degradation of a host silencing factor to facilitate infection. However, the relationship between cccDNA’s chromatin and early HBx transcription state remains poorly understood. Using reconstituted viral chromosomes, we found that nucleosomes in cccDNA drive HBx transcription. We corroborated these findings in cells and further showed that chromatin destabilizing drugs inhibit viral transcription and antigen expression in hepatocytes. Our results shed new light on a long-standing paradox and represent a novel therapeutic avenue for the treatment of chronic HBV.
2023-03-03 | GSE225714 | GEO
Project description:Chronic hepatitis B virus (HBV) remains to be the most common risk factor of hepatocellular carcinoma (HCC). While work has primarily focussed on understanding the direct and indirect mechanisms of Hepatitis B virus X protein (HBx) mediated hepatocarcinogenesis, from genetic and epigenetic perspectives, its influence on RNA modification mediated onset of liver malignancies is less well understood. This study explored the role of HBV-encoded HBx in altering the m6A methylome profile and its implications on the pathogenesis of HCC. We established HBx expressing stable HCC cell lines, Huh7-HBx and HepG2-HBx, and explored the transcriptomic and epitranscriptomic profiles by RNA-seq and MeRIP-seq, respectively. Preliminary results suggest that HBx promotes liver cell proliferation, migration, survival and overall m6A methylation in HCC cells and is involved in modulating the extracellular matrix. We show that HBx mediates liver cell transformation by upregulating KIAA1429 methyltransferase. HBx also drives the expression and hypermethylation of the extracellular matrix protein HSPG2/Perlecan and promotes tumourigenesis. Our findings indicate a potential interaction between KIAA1429 and HSPG2, thus could be novel targets in combating HBx-driven HCC and warrants further investigation.
2023-08-09 | GSE240394 | GEO
Project description:Chronic hepatitis B virus (HBV) remains to be the most common risk factor of hepatocellular carcinoma (HCC). While work has primarily focussed on understanding the direct and indirect mechanisms of Hepatitis B virus X protein (HBx) mediated hepatocarcinogenesis, from genetic and epigenetic perspectives, its influence on RNA modification mediated onset of liver malignancies is less well understood. This study explored the role of HBV-encoded HBx in altering the m6A methylome profile and its implications on the pathogenesis of HCC. We established HBx expressing stable HCC cell lines, Huh7-HBx and HepG2-HBx, and explored the transcriptomic and epitranscriptomic profiles by RNA-seq and MeRIP-seq, respectively. Preliminary results suggest that HBx promotes liver cell proliferation, migration, survival and overall m6A methylation in HCC cells and is involved in modulating the extracellular matrix. We show that HBx mediates liver cell transformation by upregulating KIAA1429 methyltransferase. HBx also drives the expression and hypermethylation of the extracellular matrix protein HSPG2/Perlecan and promotes tumourigenesis. Our findings indicate a potential interaction between KIAA1429 and HSPG2, thus could be novel targets in combating HBx-driven HCC and warrants further investigation.
2023-08-09 | GSE240450 | GEO
Project description:Hepatitis B Virus (HBV) remains a major public health problem, and is a major cause liver cancer worldwide. HBV infection in vivo requires the function of the HBx protein, which facilitates expression of viral genes from the episomal genome by an unknown mechanism. Evidence suggests that HBx functions as a targeting subunit for the CRL4 E3 ubiquitin ligase, redirecting the complex to target and degrade an unknown host restriction factor. We used substrate trapping proteomics to search for ubiquitylation substrates of HBx. We used MLN4924 to block CRL activity and stabilize interactions between HBx and its substrates. We then performed APMS to identify bound proteins and potential substrates.
2016-09-29 | PXD004762 | Pride
Project description:Hepatitis B virus (HBV) infection could cause hepatitis, liver cirrhosis and hepatocellular carcinoma. HBV-mediated pathogenesis is only partially understood, but X protein (HBx) reportedly possesses oncogenic potential. Exosomes are small membrane vesicles with diverse functions released by various cells including hepatocytes, and HBV harnesses cellular exosome biogenesis and export machineries for virion morphogenesis and secretion. Therefore, HBV infection might cause changes in exosome contents with functional implications for both virus and host. In this project, exosome protein content changes induced by HBV and HBx were quantitatively analyzed by SILAC/LC-MS/MS. Exosomes prepared from SILAC-labeled hepatoma cell line Huh-7 transfected with HBx, wildtype or HBx-null HBV replicon plasmids were analyzed by LC-MS/MS.
2017-03-29 | MSV000080794 | MassIVE
Project description:Hepatitis B virus (HBV) infection promotes liver cancer initiation by inducing inflammation and cellular stress, but its impact in established tumors is not well understood. We used affinity purification mass spectrometry to comprehensively map a network of 145 physical interactions between HBV and human proteins in hepatocellular carcinoma (HCC). A subset of the host factors targeted by HBV proteins are preferentially mutated in non-HB¬V-associated HCC suggesting that their interaction with HBV influences HCC biology. These include proteins involved in mRNA splicing, mitogenic signaling and DNA repair, with the latter set interacting with the HBV oncoprotein X (HBx). We show that HBx remodels the PP2A phosphatase complex by excluding striatin regulatory subunits from the PP2A holoenzyme. We find that HBx effects on PP2A cause Hippo kinase activation, particularly in cells with high striatin levels. In parallel, HBx activates mTOR complex 2 (mTORC2) to prevent YAP degradation. mTORC2 effects on YAP can be observed in human HCC specimens and mouse HCC models and can be targeted with mTOR kinase inhibitors. Thus, HBV interaction with host proteins rewires HCC signaling rather than directly activating mitogenic pathways. These findings provide a new paradigm for the cellular effects of a tumor promoting virus and support a model where HBV may have therapeutic actionable effects on HCC biology.
2024-11-23 | PXD055366 | Pride
Project description:In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication and acts as host gene trans-regulator. However, functionally relevant spatiotemporal localization and interactions of cccDNA and HBx remain to be understood. This is the first study utilizing circularized chromosome conformation capture (4C) to identify regional virus-host genome interactions. We combined 4C with RNA-seq and ChIP-seq to illuminate the nuclear landscape associated with HBV episomes and HBx. Moreover, we functionally studied HBx-binding to episomal HBV DNA. In human HBV-positive HepaRG hepatocytes, 4C and ChIP revealed specific nuclear localization of HBV episomes and HBx associated with actively transcribed nuclear domains correlating well in size with constrained topological units built up by chromatin fibre loops, which are believed to constitute fundamental cell nuclear architectural units. Interestingly, HBx alone occupied transcribed chromatin domains, and its binding to HBV episomes depended on its C-terminus in vitro. In conclusion, HBx and HBV DNA similarly follow higher-order nuclear assembly patterns, specifically favoring transcriptionally active nuclear compartments. These novel observations may shed light on important unsolved problems: to understand the long-term episomal stability and the facilitation of viral persistence.
2018-04-30 | GSE100400 | GEO