RNA-seq analysis of EBV transformation of primary resting B cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA518137 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8514720.fastq.gz | Fastqsanger.gz | |||
| SRR8514730.fastq.gz | Fastqsanger.gz | |||
| SRR8514721.fastq.gz | Fastqsanger.gz | |||
| SRR8514731.fastq.gz | Fastqsanger.gz | |||
| SRR8514722.fastq.gz | Fastqsanger.gz |
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Project description:RNA profile changes in primary resting B cells after EBV infection
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Project description:Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) provide a conveniently accessible and renewable resource for functional studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. A lingering concern, however, is that the changes associated with EBV transformation of LCLs reduce the usefulness of LCLs as a surrogate model for primary tissues. To evaluate the validity of this concern, we compared global promoter CpG profiles between CD20+ primary B cells and CD3+ primary T cells sampled from six individuals. Six independent replicates of transformed LCLs were derived from each sample.
2011-03-01 | GSE26211 | GEO
Project description:Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) provide a conveniently accessible and renewable resource for functional studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. A lingering concern, however, is that the changes associated with EBV transformation of LCLs reduce the usefulness of LCLs as a surrogate model for primary tissues. To evaluate the validity of this concern, we compared global gene expression profiles between CD20+ primary B cells and CD3+ primary T cells sampled from six individuals. Six independent replicates of transformed LCLs were derived from each sample.
2011-03-01 | GSE26210 | GEO
Project description:Background: In several types of malignancies, especially EBV-associated nasopharyngeal carcinomas, high Galectin-9 (Gal-9) expression is indicative of an aggressive tumor phenotype. The contribution of Gal-9 to the oncogenesis of B-cell lymphomas (BCLs) has not yet been investigated. Methods: The expression of Gal-9, STING, and EBNA1 was measured by immunohistochemical (IHC) staining on tumor sections from 66 BCL patients. Artificial EBV infection of normal primary B cells in vitro was used as an experimental model. The dynamic changes of the transcriptome of EBV-infected B cells undergoing transformation were investigated by bulk RNA-sequencing and bioinformatics analysis. The oncogenic role of Gal-9 was investigated in vitro by addition of recombinant Gal-9 to EBV-infected primary B-cells, and growth assays. The underlying molecular mechanisms were investigated by immunoblotting and immunofluorescent (IF) staining, CHIP and luciferase reporter assays. Results: In clinical specimens of BCLs, Gal-9 expression was significantly associated with tumor stage, latent EBV infection and abundance of the viral latent protein EBNA1. Looking at the transcriptome changes occurring in vitro during EBV-driven B-cell transformation, we could identify a series of genes undergoing long term activation and remaining highly expressed in mature LCLs. The Gal-9 gene is one of them. Its expression is enhanced during the transformation process at the mRNA level and even more at the protein level. This up-regulation results at least in part from its transactivation by EBNA1 which can bind its promoter. Reciprocally, we find that addition of extra-cellular Gal-9 promotes B-cell transformation and establishment of the latent phase of EBV-infection. Concomitantly, extra-cellular Gal-9 blocks STING signaling and enhances STAT3 phosphorylation. Inhibition of Sting signaling or STAT3 phosphorylation blocks B-cell transformation, even in the presence of Gal-9. Conclusion: our data unveil a role of amplification and acceleration for Gal-9 in the process of EBV-driven B-cell transformation. This process might be relevant to the pathogenesis of EBV-associated BCLs.
2022-06-30 | GSE162516 | GEO
Project description:<p>Following infection of B cells, Epstein Barr virus (EBV) engages host pathways that mediate cell proliferation and transformation, contributing to the propensity of the virus to drive immune dysregulation and lymphomagenesis. We found that the EBV protein EBNA2 initiates NAD <em>de novo</em> biosynthesis by driving expression of the host metabolic enzyme IDO1. Virus-enforced NAD production sustained mitochondrial complex I activity, to match ATP-production with bioenergetic requirements of proliferation and transformation. In transplant patients, IDO1 expression in EBV-infected B cells, and a serum signature of increased IDO1 activity, preceded development of lymphoma. In humanized mice infected with EBV, IDO1 inhibition reduced both viremia and lymphomagenesis. Virus-orchestrated NAD biosynthesis is thus a druggable metabolic vulnerability of EBV-driven B cell transformation – opening therapeutic possibilities for EBV-related diseases.</p>
2024-04-29 | MTBLS2243 | MetaboLights
Project description:Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) provide a conveniently accessible and renewable resource for functional studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. A lingering concern, however, is that the changes associated with EBV transformation of LCLs reduce the usefulness of LCLs as a surrogate model for primary tissues. To evaluate the validity of this concern, we compared global gene expression profiles between CD20+ primary B cells and CD3+ primary T cells sampled from six individuals. Six independent replicates of transformed LCLs were derived from each sample. The study included 96 RNA samples: 8 different types (B cell + T cell + 6 independent LCLs per individual) x 6 individuals x 2 technical replicates (each RNA sample hybridized in duplicate).
2011-03-01 | E-GEOD-26210 | biostudies-arrayexpress
Project description:Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) provide a conveniently accessible and renewable resource for functional studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. A lingering concern, however, is that the changes associated with EBV transformation of LCLs reduce the usefulness of LCLs as a surrogate model for primary tissues. To evaluate the validity of this concern, we compared global promoter CpG profiles between CD20+ primary B cells and CD3+ primary T cells sampled from six individuals. Six independent replicates of transformed LCLs were derived from each sample. The study included 96 DNA samples: 8 different types (B cell + T cell + 6 independent LCLs per individual) x 6 individuals x 2 technical replicates (each DNA sample hybridized in duplicate).
2011-03-01 | E-GEOD-26211 | biostudies-arrayexpress
Project description:B cells from anonymous adenoid donors were isolated and sorted for naïve B cells, which were subsequently infected with a reference EBV strain (2089_B95-8) using a defined multiplicity of infection. Infection of resting B cells with EBV induces their activation, their proliferation, and subsequent immortalization giving rise to lymphoblastoid cell lines (LCL) in vitro. Non-infected primary B-lymphocytes immediately after preparation (day 0) and at early time points post infection (day 1, 2, 3, 4, 5, 8, and 14) were collected and total RNAs were prepared. We performed time course RNA-seq experiments and assessed the expression kinetics of viral (EBV_2089) and cellular genes (Hg19) in these cells that show impressive phenotypic alterations over time. The experiment revealed the very dynamic regulation of viral and cellular genes that could be grouped into six clusters of transcriptional regulation documenting the cellular response to viral infection and the virally induced cell reprogramming and transformation.
2019-07-01 | E-MTAB-7805 | biostudies-arrayexpress
Project description:In order to gain insights into the intricate molecular alterations taking place following Epstein-Barr virus (EBV) infection in primary B-cells, we employed RNA-Seq to investigate the dynamic changes occurring within the cell transcriptome during the early stages of EBV infection (0, 2, and 4 days post infection). By analysing the transcriptomic data generated, our objective was to find novel pathways and mechanisms that may play pivotal roles in the EBV-induced transformation of B-cells, particularly during early stage of B-cell activation.
2023-08-03 | GSE235941 | GEO
Project description:Epstein-Barr Virus (EBV) is associated with numerous cancers including B cell lymphomas. In vitro, EBV transforms primary B cells into immortalized Lymphoblastoid Cell Lines (LCLs) which serves as a model to study the role of viral proteins in EBV malignancies. EBV induced cellular transformation is driven by viral proteins including EBV-Nuclear Antigens (EBNAs). EBNA-LP is important for the transformation of naïve but not memory B cells. While EBNA-LP was thought to promote gene activation by EBNA2, EBNA-LP Knock Out (LPKO) virus-infected cells express EBNA2-activated cellular genes efficiently. Therefore, a gap in knowledge exists as to what roles EBNA-LP plays in naïve B cell transformation. We developed a trans-complementation assay wherein transfection with wild-type EBNA-LP rescues the transformation of peripheral blood- and cord blood-derived naïve B cells by LPKO virus. Despite EBNA-LP phosphorylation sites being important in EBNA2 co-activation; neither phospho-mutant nor phospho-mimetic EBNA-LP was defective in rescuing naïve B cell outgrowth. However, we identified conserved leucine-rich motifs in EBNA-LP that were required for transformation of adult naïve and cord blood B cells. Because cellular PPAR-g coactivator (PGC) proteins use leucine-rich motifs to engage transcription factors including YY1, a key regulator of DNA looping and metabolism, we examined the role of EBNA-LP in engaging cellular transcription factors. We found a significant overlap between EBNA-LP and YY1 in ChIP-Seq data. By Cut&Run, YY1 peaks unique to WT compared to LPKO LCLs occur at more highly expressed genes. Moreover, Cas9 knockout of YY1 in primary B cells prior to EBV infection indicted YY1 to be essential for EBV-mediated transformation. We confirmed EBNA-LP and YY1and confirmed their biochemical association in LCLs by endogenous co-immunoprecipitation and. Moreover, we found that the EBNA-LP leucine-rich motifs were required for YY1 interaction in LCLs. Finally, we used Cas9 to knockout YY1 in primary total B cells and naïve B cells prior to EBV infection and found YY1 to be essential for EBV-mediated transformation. We propose that EBNA-LP engages YY1 through conserved leucine-rich motifs to promote EBV transformation of naïve B cells.
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