Hepatitis B virus genotype A
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB10091 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| DRR234478_1.fastq.gz | Fastqsanger.gz | |||
| DRR234478_2.fastq.gz | Fastqsanger.gz |
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Project description:Hepatitis B virus (HBV) is an enveloped, coated, non-cytopathic and hepatotropic partially double-stranded DNA virus in the family Hepadnaviridae genus Orthohepadnavirus. Despite significant progress in the availability of safe vaccines and antiviral therapies against HBV, it still affects approximately 257 million people worldwide and is responsible for about 887,000 deaths per year around the world [4]. HBV infection, which are associated with acute and chronic liver failure responses to viruses attacked the liver, can result in inactive carrier state, chronic hepatitis, or fulminant hepatitis and put them at high risk to develop advanced liver fibrosis and cirrhosis, and even hepatocellular cancer. Many viral factors, which could affect the disparity of clinical outcomes or disease prognosis during chronic HBV infection, have been reported in previous studies; among them, the viral genotype, as well as HBV mutations ascribing the virus to a certain phenotype, was reported to be the most important factor influencing viral pathogenesis, including the change of host immune recognition, the enhanced virulence with increased HBV replication and the facilitation of cell attachment or penetration.
2022-02-17 | PXD025968 | Pride
Project description:The presentation of virus-derived peptides by HLA class I molecules on the surface of an infected cell and the recognition of these HLA-peptide complexes by, and subsequent activation of, CD8+ cytotoxic T cells provides an important mechanism for immune protection against viruses. Recent advances in proteogenomics have allowed researchers to discover a growing number of unique HLA-restricted viral peptides, resulting in a rapidly expanding repertoire of targets for immunotherapeutics (i.e. bispecific antibodies, engineered T-cell receptors (TCRs), chimeric antigen receptor T-cells (CAR-Ts)) to infected tissues. However, genomic variability between viral strains, such as Hepatitis-B virus (HBV), in combination with differences in patient HLA alleles, make it difficult to develop therapeutics against these targets. To address this challenge, we developed a novel proteogenomics approach for generating patient-specific databases that enable the identification of viral peptides based on the viral transcriptomes sequenced from individual patient liver samples. We also utilized DNA sequencing of patient samples to identify HLA genotypes and assist in target selection. Liver samples from 48 HBV infected patients, primarily from Asia, were examined to reconstruct patient-specific HBV genomes, identify regions within the human chromosomes targeted by HBV integrations and obtain a comprehensive view of HBV peptide epitopes using our HLA class-I (HLA-I) immunopeptidomics discovery platform. Two previously reported HLA associated HBV-derived peptides, HLA-A02 binder FLLTRILTI (S194-202) from the large surface antigen and HLA-A11 binder STLPETTVVRR (C141-151) from the capsid protein were validated by our discovery platform, but both were detected at a very low frequencies. In addition, we identified and validated, using heavy peptide analogues, novel strain-specific HBV-HLA associated peptides, such as GSLPQEHIVQK (P606-616) and variants. Overall, our novel approach can guide the development of bispecific antibody, TCR-T, or CAR-T based therapeutics for the treatment of HBV-related HCC and inform vaccine development.
2023-01-03 | PXD037270 | Pride
Project description:Hepatitis B Virus (HBV) is a small DNA virus that replicates via an episomal covalently closed circular DNA (cccDNA) that serves as the transcriptional template for viral mRNAs. The host protein, CCCTC-binding factor (CTCF), is a key regulator of cellular transcription by maintaining epigenetic boundaries, nucleosome phasing, stabilisation of long-range chromatin loops and directing alternative exon splicing. We previously reported that CTCF binds two conserved motifs within Enhancer I of the HBV genome and represses viral transcripts, however, the underlying mechanisms were not identified. We show that CTCF depletion in cells harbouring cccDNA-like HBV molecules and in de novo infected cells resulted in an increase in spliced transcripts, which was most notable in the abundant SP1 spliced transcript. In contrast, depletion of CTCF in cell lines with integrated HBV DNA had no effect on the abundance of viral transcripts and in line with this observation there was limited evidence for CTCF binding to viral integrants, suggesting that CTCF-regulation of HBV transcription is specific to episomal cccDNA. Analysis of HBV chromatin topology by Assay for Transposase Accessibility/sequencing (ATAC-Seq) revealed an accessible region spanning Enhancers I and II and the basal core promoter (BCP). Mutating the CTCF binding sites within Enhancer I resulted in a dramatic rearrangement of chromatin accessibility where the open chromatin region was no longer detected, indicating loss of the phased nucleosome up- and down- stream of the HBV enhancer/BCP. These data demonstrate that CTCF functions to regulate HBV chromatin conformation and nucleosomal positioning in episomal maintained cccDNA, which has important consequences for HBV transcription regulation.
2024-01-18 | GSE248738 | GEO
Project description:Background & Aims: Hepatitis B virus (HBV) infection is a major health burden worldwide and currently there is no cure. The persistence of HBV covalently closed circular DNA (cccDNA) is the major obstacle for antiviral treatment. HBV core protein (HBc) has merged as a promising antiviral target, as it plays important roles in critical steps of viral life cycle. However, whether HBc could regulate HBV cccDNA transcription remains to be illustrated. Methods: Synthesized HBV cccDNA and HBVcircle with or without HBc deficiency were transfected into hepatocytes. A recently reported Adeno-Associated Virus (AAV) mediated HBV cccDNA mouse model was employed. Two capsid assembly modulators (CAMs) were used. HBV replication markers were evaluated. Chromatin immunoprecipitation (ChIP) or ChIP sequencing assays were conducted with different transcription factors, histones and RNA polymerase 2. Results: In HBV cccDNA and HBVcircle transfection assays, lack of HBc showed no effect on transcription of HBV RNA as well as HBV surface antigen production. Reconstitution of HBc did not change cccDNA derived HBV markers. Similar results were obtained in vivo, from mouse cccDNA model. ChIP data revealed similar transcription regulation of HBc deficient cccDNA chromatin with wide type cccDNA. Furthermore, CAMs treatment could not alter cccDNA transcription. Conclusions: Our results indicate that HBc neither affects histone modifications and transcription factors binding of cccDNA, nor influences cccDNA transcription. Although CAMs could reduce HBc binding to cccDNA, it does not suppress cccDNA transcriptional activity. Thus, therapeutic targeting capsid or HBc is not sufficient to reduce cccDNA transcription.
2022-04-01 | GSE199653 | GEO
Project description:Curing treatment for HBV infection is yet unavailable, mainly due to unmet gaps in current understanding of the details about HBV-host interaction. By quantitatively assessing HBV-induced global changes in host transcriptome, translatome and proteome, we identified multiple previously unknown transcriptional and translational events that HBV orchestrated to remodel host proteostasis networks and afford micro-environments essential for HBV proliferation and persistence.By delineating novel drug targets and biomarkers in HBV-host interaction, multi-omics interrogation may facilitate the development of next-generation therapeutics or diagnostics against HBV infection and the related maladies.
2021-03-06 | GSE135860 | GEO
Project description:Chronic hepatitis B virus (HBV) infection is an incurable global health threat responsible for causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent minichromosome consisting of the viral covalently closed circular DNA (cccDNA) genome and host histones. The viral X gene must be expressed immediately upon infection to induce degradation of the host silencing factor, Smc5/6. However, the relationship between cccDNA chromatinization and X gene transcription remains poorly understood. Establishing a reconstituted viral minichromosome platform, we found that nucleosome occupancy in cccDNA drives X transcription. We corroborated these findings in cells and further showed that the chromatin destabilizing molecule CBL137 inhibits X transcription and HBV infection in hepatocytes. Our results shed light on a long-standing paradox and represent a potential new therapeutic avenue for the treatment of chronic HBV infection.
2024-06-19 | GSE270130 | GEO
Project description:Molecular characterization of Hepatitis B virus (HBV) in Vietnam
| PRJNA397491 | ENA
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 | GSE225715 | GEO
Project description:Phosphorylation is a major post-translation modification (PTM) of proteins, and small molecules, which is finely tuned by the activity of several hundred kinases and phosphatases. It controls most if not all cellular pathways including anti-viral responses. Accordingly, viruses often induce important changes in the phosphorylation of host factors that can either help or counteract viral replication. Surprisingly, among more than 500 kinases constituting the human kinome only few have been described as important for the Hepatitis B virus (HBV) infectious cycle, and most of them intervene during early or late infectious steps by phosphorylating the viral Core protein (HBc) protein. In addition, scarce information is available on the consequences of HBV infection on the activity of cellular kinases. The objective of this study was to investigate the global impact of HBV infection on the cellular phosphorylation landscape at early after infection. For this, primary human hepatocytes (PHH) were challenged or not with HBV, and a mass spectrometry (MS)-based quantitative phospho-proteomic analysis was conducted two- and seven-days post-infection.
2024-05-02 | PXD051216 | Pride