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.
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Project description:Epstein-Barr virus (EBV) is a human herpesvirus that has been associated with the development of human cancers across the globe. In laboratory settings, the virus efficiently infects resting human B lymphocytes, inducing their growth transformation and leading to the establishment of lymphoblastoid cell lines (LCLs) within a few weeks. This process is accompanied by a global reprogramming of cellular gene transcription. A systematic time-resolved analysis of cellular mRNA splice variant expression during EBV infection of resting B lymphocytes has previously been performed. The results demonstrated that significant alterations in alternative splice variant expression occur as early as day 1 post-infection, indicating that splicing regulation, in addition to transcription, represents an additional mechanism of gene expression regulation at the onset of B cell activation and proliferation. The present study had two principal objectives. The first was to identify which transcriptional and splice events are specific to the EBV infection, in comparison to the activation of primary B lymphocytes by a combination of CD40 ligand (CD40L) and interleukin 4 (IL4). The second was to ascertain which events are dependent on the EBNA2 and EBNALP viral factors. In order to achieve these objectives, a comparative RNA-seq analysis of the transcriptome of the infected cells or those treated with CD40L/IL4, as well as LCLs derived from the wild-type and EBNALP KO EBV-infected cells, was conducted.
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2023-08-03 | GSE235941 | GEO