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Project description:RNA-seq analysis of EBV transformation of primary resting B cells
| PRJNA518137 | ENA
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:Purpose: Immediate-early protein BRLF1 plays an important role in lytic infection of Epstein-Barr virus (EBV), it activates lytic viral transcription and viral DNA replication, affects cell cycle and suppresses inflammatory responses. However, the understanding of BRLF1 influence on cellular gene expression during early lytic cycle remains limited. Methods:RNA-sequencing analysis identified the differentially expressed genes (DEGs) in B lymphoma cells undergoing wild type and BRLF1-deficient EBV primary infection. The libraries were sequenced on an Illumina HiSeq-Xten platform and 150 bp paired‐end reads were generated. An average read depth of 12G reads per sample was collected and analyzed. Data analysis was performed with Molecule Annotation System 3.0. Results: A total of 159 unigenes were annotated and the major differentially enriched pathways were related to DNA replication and transcription, immune and inflammatory response, cytokine-receptor interaction and chemokine signaling, ECM-receptor interaction and focal adhesion. Further the mass spectrometry identified the BRLF1-binding proteins and showed that BRLF1 employed different strategies to influence RNA polymerase II-dependent viral and cellular transcription, by binding to a particular RREs motif and binding to unique transcription factors which binding to specific motifs. Conclusions: Our study characterized the BRLF1-dependent cellular and viral transcriptional profile during primary infection and then revealed the important virus-cell interaction and alterations of cell activity for EBV primary infection and lytic replication.
2020-08-30 | GSE154786 | 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:Epstein Barr virus causes linfectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. These anlyses were undertaken in order to determine what gene expression changes occur as the result of primary Epstein Barr virus infection. Samples were taken both before and following acquisition of the virus for direct comparison of samples for single subjects. These data provide an important first description of the response to natural herepesvirus infection in humans. PBMC were taken before acquisition of EBV, during acute infection, and during latency
2013-12-31 | E-GEOD-45918 | biostudies-arrayexpress
Project description:Epstein Barr virus causes linfectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. These anlyses were undertaken in order to determine what gene expression changes occur as the result of primary Epstein Barr virus infection. Samples were taken both before and following acquisition of the virus for direct comparison of samples for single subjects. These data provide an important first description of the response to natural herepesvirus infection in humans. PBMC were taken before acquisition of EBV, during acute infection, and during latency
2013-12-31 | E-GEOD-45919 | biostudies-arrayexpress
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) is an oncogenic virus that is associated with the pathogenesis of several human lymphoid malignancies, including Hodgkin's lymphoma. Infection of normal resting B cells with EBV results in activation to lymphoblasts that are phenotypically similar to those generated by physiological stimulation with CD40L plus IL-4. One important difference is that infection leads to the establishment of permanently growing lymphoblastoid cell lines, whereas CD40L/IL-4 blasts have finite proliferation life-spans. To identify early events which might later determine why EBV infected blasts go on to establish transformed cell lines, we performed global transcriptome analyses on resting B cells and on EBV and CD40L/IL-4 blasts after 7 days culture. As anticipated, there was considerable overlap in the transcriptomes of the two types of lymphoblasts when compared to the original resting B cells, reflecting common changes associated with lymphocyte activation and proliferation. Of interest to us was a subset of 225 genes that were differentially expressed between EBV and CD40/IL4- blasts. Genes which were more highly expressed in EBV blasts were substantially and significantly enriched for a set of interferon-stimulated genes which on further in silico analyses were found to be repressed by IL-4 in other cell contexts and to be up-regulated in micro-dissected malignant cells from Hodgkin's lymphoma biopsies when compared to their normal germinal center cell counter parts. We hypothesized that EBV and IL-4 were targeting and discordantly regulating a common set of genes. This was supported experimentally in our model where IL-4 stimulation partially reversed transcriptional changes which follow EBV infection and it impaired the efficiency of EBV-induced B cell transformation. Taken together, these data suggest that discordant regulation of interferon and IL-4 pathway genes by EBV that occurs early following infection of B cells has relevance to the development or maintenance of an EBV-associated malignancy. 9 samples were analysed and these included 3 biological replicates of the following samples: primary B cells isolated by positive selection using CD19+ Dynabeads and harvested immediately for RNA and primary B cells infected with EBV or stimulated with CD40L and IL4 and harvested 7 days post-infection/ cytokine stimulation. All biological replicates represent B cells which were pooled from 3 or 4 different buffy coat donors.
2014-02-03 | E-GEOD-45829 | 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)-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