Full-length deep sequencing of South African Hepatitis B Virus (HBV) reveals increased diversity and frequent deletions in adults with hepatocellular carcinoma (HCC)
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PROVIDER: PRJEB59095 | ENA |
REPOSITORIES: ENA
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Project description:HBV sequence motif associated with HCC in Sth African adults
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Project description:In this study, we collected both the tumors and tumor-adjacent tissues from HBV-positive and HBV-negative HCC patients, conducted scRNA-seq, and compared the immune microenvironment of HBV-positive and HBV-negative tumors.
2025-01-01 | GSE282701 | GEO
Project description:Global expression profiling of miRNAs in liver tissue of HBV infected HCC and chronic hepatitis B (CHB) with no fibrosis was evaluated. A total of 40 differentially expressed miRNAs were identified in HCC. Top 10 miRNAs are validated in more numbers of HCC tisuues by qRT PCR. Finally six miRNAs (miR-15a, miR-16, miR-21,miR-29b-3p, miR-126, miR-142-3p, miR-193a-5p) showed similar expression pattern in both microarray and qRT PCR Differential expression analysis of microRNAs in HBV infected HCC (n=4) compared to CHB patients with no fibrosis (n=8) as control.
2015-04-15 | E-GEOD-67882 | biostudies-arrayexpress
Project description:This study aimed to better characterize the repertoire of serum HBV RNAs during chronic HBV infection in humans, which remains understudied. Using RT-PCR, qPCR, RNA-sequencing and immuno-precipitation, we found that (i) >50% of serum samples bore different amounts of HBV replication-derived RNAs (rd-RNAs); (ii) a few samples contained RNAs transcribed from integrated HBV DNA including 5'-HBV-human-3' RNAs (integrant-derived RNAs or id-RNAs) and 5'-human-HBV-3' transcripts as a minority of serum HBV RNAs; (iii) spliced HBV RNAs were abundant in <50% of analyzed samples; (iv) most serum rd-RNAs were polyadenylated via conventional HBV polyadenylation signal; (v) pre-genomic RNA (pgRNA) was the major component of the pool of serum RNAs; (vi) area of HBV positions 1531-1739 had very high RNA reads coverage and thus should be used as a target for detecting serum HBV RNAs; (vii) vast majority of rd-RNAs and pgRNA were associated with HBV virions, but not with unenveloped capsids, exosomes, classic microvesicles or apoptotic vesicles and bodies; (viii) considerable rd-RNAs presence in the circulating immune complexes was found in a few samples; and (ix) serum rcDNA and rd-RNAs should be quantified simultaneously to evaluate HBV replication status and efficacy of anti-HBV therapy with nucleos(t)ide analogs. In summary, sera contain various HBV RNA types of different origin, which are likely secreted via different mechanisms. In addition, since we previously showed that id-RNAs were abundant or predominant HBV RNAs in many of liver and hepatocellular carcinoma tissues comparing to rd-RNAs, there is likely a mechanism favoring the egress of the replication-derived RNAs.
2023-02-26 | GSE224901 | GEO
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:MicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. As such miRNA signatures are valuable as biomarkers for disease and for making treatment decisions. Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Here we screened for miRNAs in chronic HBV associated HCC. To evaluate the effect of HBV infection on the change in expression of miRNAs, 12 pairs of samples from HCC and non-tumor tissues (including 6 HBV-positive HCC and 6 HBV-negative HCC and their non-tumor tissues) were collected. The extracted RNAs were evaluated to detect the expression of miRNAs. Using ANOVA to screen the differential expression of miRNAs at P-value ⤠0.01, fold change ⥠2 or ⤠0.5, 225 miRNAs were detected.
2016-06-30 | E-MTAB-4809 | biostudies-arrayexpress
Project description:Global expression profiling of miRNAs in liver tissue of HBV infected HCC and chronic hepatitis B (CHB) with no fibrosis was evaluated. A total of 40 differentially expressed miRNAs were identified in HCC. Top 10 miRNAs are validated in more numbers of HCC tisuues by qRT PCR. Finally six miRNAs (miR-15a, miR-16, miR-21,miR-29b-3p, miR-126, miR-142-3p, miR-193a-5p) showed similar expression pattern in both microarray and qRT PCR
2015-04-15 | GSE67882 | GEO
Project description:Purpose: Chronic infection with hepatitis B virus is the leading global risk factor for the development of liver cancer. A large body of research has shown the many effects an HBV infection has on cellular physiology, particularly on pathways that may be involved in the development of HBV-associated diseases. Unfortunately, a significant portion of this research has been done in systems that may not mimic what is seen in a primary hepatocyte, and is not done on a transcriptome-wide scale. Because of this, we performed an RNA-seq analysis of primary rat hepatocytes either expressing HBV or not over a series of time points to determine the global changes HBV has on primary hepatocyte physiology. Methods: To do this RNA-seq analysis, triplicate samples of total RNA were collected from cultured primary rat hepatocytes (PRH) over the course of 72hr. PRH were collected immediately after isolation (0hr), or 24hr, 48hr, or 72hr after plating. In addition, PRH were infected 24hr after plating with adenovirus expressing GFP alone (AdGFP) or GFP along with a greater than unit length copy of the HBV genome (AdHBV) and collected at 48hr after plating (24hr after infection) or 72hr after plating (48hr after infection). cDNA libraries were sequenced using the Illumina NextSeq 500 platform to generate either 1x75bp reads. Reads were mapped using the STAR aligner, and output BAMs were further analyzed in R using the GenomicAlignments package, to quantify number of reads per transcript, and DESeq2, to determine differential expression. Reads per kilobase transcript per million total reads (RPKM) was calculated by dividing reads per transcript by the transcript length and then normalizing to the total number of reads in the sample. Results: Following this pipeline, we were able to identify a number of HBV-mediated differentially expressed transcripts at 48hr and 72hr. In addition, we noted considerable change to the hepatocyte transcriptome as a direct result of the isolation/plating procedure, regardless of the presence of HBV. Further pathway analysis of these differentially expressed transcripts identified many important cellular pathways, including those involved with cell cycle regulation and metabolism, as being differentially regulated by HBV in primary hepatocytes. mRNA profiles of cultured primary rat hepatocytes were generated, in triplicate, using the Illumina NextSeq 500 platform from freshly isolated cells (0hr), 24hr, 48hr, or 72hr after plating, and with or without expression of HBV 48hr or 72hr after plating.
2016-01-20 | E-GEOD-68112 | biostudies-arrayexpress
Project description:In the study, we identified protein arginine methyltransferase 5 (PRMT5) as a novel restriction factor of HBV replication. We have also demonstrated that PRMT5 can interact with the HBV core and methylate its arginine residues within arginine-rich domain. We identified two types of HBc post-translational modifications: arginine methylation and ubiquitination. While monomethylated HBc retains cytoplasmic localization, symmetric dimethylation is linked to serine phosphorylation and nuclear transport. Thus arginine methylation and ubiquitination are novel types of HBc post-translational modifications which add another level of complexity to the understanding of HBc function and regulation of HBV replication
2017-11-01 | PXD006828 | Pride
Project description:Hepatitis B virus isolate:HBV 003 Genome sequencing
| PRJNA289732 | ENA