Epstein Barr Virus genomes in endemic Burkitt lymphoma tumors
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB38735 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4222580_1.fastq.gz | Fastqsanger.gz | |||
| ERR4222580_2.fastq.gz | Fastqsanger.gz | |||
| ERR4222590_1.fastq.gz | Fastqsanger.gz | |||
| ERR4222590_2.fastq.gz | Fastqsanger.gz | |||
| ERR4222600_1.fastq.gz | Fastqsanger.gz |
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Project description:Whilst the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognized, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. We have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. Whilst loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. We investigated whether there were common gene expression changes between EBV-positive and loss clones derived for four endemic Burkitt lyphoma cell lines that could explain the apoptosis sensitivity of clones that had lost EBV.
2018-01-25 | GSE100458 | GEO
Project description:<p>This genomic landscape of Burkitt lymphoma represents a multimodal sequencing of tumors and control tissues and individuals to better understand the etiology, and molecular pathogenesis of Burkitt lymphoma including the roles of the associated Plasmodium falciparum malaria and EBV infections. Comprehensive sequencing set includes genomic, transcriptomic, and epigenomic datasets in concert with variable clinical phenotypes and outcome information such as anatomical presentation site, in-hospital survival rates, and EBV genome type. The initial deposit represents polyA RNA-seq from tumor specimens from 28 cases of endemic BL and 2 cases of sporadic BL.</p> <p><b>For initial transcriptome analysis see: Kaymaz et al.</b> Comprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals EBV Type-specific Difference. Molecular Cancer Research: MCR, January. doi:10.1158/1541-7786.MCR-16-0305.<br/> <b>For general overview of cohort study see:</b> Buckle et al. Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study. Int J Cancer. 15:1231, 2016.</p>
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Project description:Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma and immunosuppression-related lymphomas. These B-cell malignancies arise by distinct transformation pathways and utilize divergent viral and host expression programs. To identify host dependency factors elicited by EBV latent-infection states, we performed parallel genome-wide CRISPR/Cas9 screens in Burkitt lymphoma (BL) and lymphoblasotid cell lines (LCL). Our results highlighted 57 BL and 87 LCL genes selectively critical for their growth and survival. LCL hits were enriched for EBV-induced genes, including viral super-enhancer targets and multiple kinases. We uncovered key CD19/CD81 roles in EBV membrane protein-driven PI3K/AKT activation and mechanisms by which EBV evades tumor suppressor responses to its growth program. LMP1-induced cFLIP was critical for LCL defense against TNFa-mediated programmed cell death, while EBV-induced BATF/IRF4 were critical for LCL BIM suppression and MYC induction. EBV super-enhancer targeted IRF2 protected LCLs against BLIMP1 responses. Collectively, our results identify host/pathogen interaction-driven synthetic lethal targets for therapeutic intervention.
2017-05-11 | GSE93681 | GEO
Project description:Epstein-Barr virus (EBV) causes Burkitt, Hodgkin, and post-transplant B-cell lymphomas. How EBV remodels metabolic pathways to support rapid B-cell outgrowth remains largely unknown. To gain insights, primary human B-cells were profiled by tandem-mass-tag based proteomics at rest and at 9 time points after infection. >8000 host and 29 viral proteins were quantified, revealing mitochondrial remodeling and induction of one-carbon (1C) metabolism. EBV-encoded EBNA2 and its target MYC were required for upregulation of the central mitochondrial 1C enzyme MTHFD2, which played key roles in EBV-driven B-cell growth and survival. MTHFD2 was critical for maintaining elevated NADPH levels in infected cells, and oxidation of mitochondrial NADPH diminished B-cell proliferation. Tracing studies underscored contributions of 1C to nucleotide synthesis, NADPH production and redox defense. EBV upregulated import and synthesis of serine to augment 1C flux. Our results highlight EBV-induced 1C as a potential therapeutic target and provide a new paradigm for viral onco-metabolism.
2019-06-28 | PXD013034 | Pride
Project description:Epstein Barr virus (EBV) replication contributes to multiple human diseases, including infectious mononucleosis, nasopharyngeal carcinoma, B-cell lymphomas, and oral hairy leukoplakia. We performed systematic quantitative analyses of temporal changes in host and EBV proteins during lytic replication to gain novel insights into virus-host interactions, using conditional Burkitt lymphoma models of type I and II EBV infection. We quantified profiles of >8000 cellular and 69 EBV proteins, including >500 plasma membrane proteins, providing temporal views of the lytic B-cell proteome and EBV virome. Our approach revealed EBV-induced remodelling of cell cycle, innate and adaptive immune pathways, including upregulation of the complement cascade and proteasomal degradation of the B-cell receptor complex, conserved between EBV types I and II. Cross-comparison with proteomic analyses of human cytomegalovirus infection and of a Kaposi sarcoma associated herpesvirus immunoevasin identified host factors targeted by multiple herpesviruses. Our results provide an important resource for studies of EBV replication.
2017-05-19 | PXD006317 | Pride
Project description:Igh/Myc translocations underlie both sporadic Burkitt lymphoma (BL) and the endemic clinical form affecting African children infected with malaria. However, while sporadic translocations decapitate Myc from 5' proximal regulatory elements, most endemic events occur hundreds of kilobases away from Myc. The origin of these rearrangements and how they deregulate oncogenes at such distances remain unclear. Here we recapitulate endemic BL-like translocations in plasmacytomas from uracil N-glycosylase (UNG) deficient mice. We demonstrate that in these animals, rare endemic-like translocations arise from non-targeted DNA breaks at Myc loci. Deep-sequencing analyses revealed that the deregulated 3' Igh enhancer alpha physically interacts with and remodels 0.45Mb of translocated chromatin. The results thus explain the long-range deregulation of oncogenes in human and mouse B cell tumors. ChIP-Seq, 4C, and 1 RNASeq samples used to characterize mouse plasmacytoma cell lines and in vitro activated mouse B cells. Biological replicates are present for many of the samples.
2013-07-04 | E-GEOD-48514 | biostudies-arrayexpress
Project description:Previously, we identified Syncytin1 to be expressed in human B cells and enhance EBV ability to undergo lytic replication. To gain mechanistic insight, we performed liquid chromatography tandem mass spectrometry (LC-MS/MS) on tryptic peptides from immunoprecipitated FLAG-tagged Syncytin-1 in latently infected EBV+ Burkitt lymphoma cells. This revealed a number of cellular proteins as potential Syncytin-1 interacting partners during latency and/or during the lytic phase as well as two EBV lytic phase proteins, the viral protein kinase and LF2, a negative regulator of EBV lytic gene transcription. We now find that Syncytin1 reduces the association between LF2 and the EBV replication and transcription activator to promote EBV lytic gene expression.
2023-05-15 | MSV000091949 | MassIVE
Project description:Transition of Akata Burkitt lymphoma (BL) cells from a malignant to nonmalignant phenotype upon loss of Epstein-Barr virus (EBV) genomes in vitro is evidence for a viral contribution to tumor maintenance despite the tightly restricted pattern of EBV gene expression in BL. Akata cells retaining virus manifest increased resistance to apoptosis under growth limiting conditions, although ambiguity exists regarding the exact mechanisms involved. By examining global cellular gene expression differences in Akata subclones that had either retained or lost EBV, we identified spermidine/spermine N1-acetyltransferase (SSAT), an inducible acetylating enzyme whose catabolism of polyamines affects both apoptosis and cell growth, as one of a limited number of cellular genes up-regulated upon loss of EBV. Keywords: Disease state analysis We used Affymetrix microarrays to examine variations in global gene expression between the paired EBV-positive (1B6) and EBV-negative (2A8) Akata Burkitt's lymphoma clones. EBV-negative Akata clones were generated by treatment with hydroxyurea, an inhibitor of ribonucleotide reductase that forced rapid loss of EBV episomes and compared to their EBV-positive counterparts. Logarithmically growing EBV-negative and positive Akata EBV clones were seeded at 2.5x10^5 cells/ml in RPMI1640 supplemented with 10% fetal bovine serum, 2mM glutamine, and 100units/ml penicillin/streptomycin. The next day, the cells were incubated for 4 hours in media containing 1% fetal bovine serum (low serum), 2mM glutatmine and 100units/ml penicillin/streptomycin to begin selection of the Akata tumor phenotype. The short incubation time was intended to minimize cell death and other potential downstream effects of low serum treatment, while at the same time initiating expression changes contributing to the tumorigenic phenotype.
2010-01-19 | E-GEOD-19761 | biostudies-arrayexpress
Project description:Expression and Mutational Analysis of Endemic Burkitt Lymphoma
| PRJNA369584 | ENA
Project description:Igh/Myc translocations underlie both sporadic Burkitt lymphoma (BL) and the endemic clinical form affecting African children infected with malaria. However, while sporadic translocations decapitate Myc from 5' proximal regulatory elements, most endemic events occur hundreds of kilobases away from Myc. The origin of these rearrangements and how they deregulate oncogenes at such distances remain unclear. Here we recapitulate endemic BL-like translocations in plasmacytomas from uracil N-glycosylase (UNG) deficient mice. We demonstrate that in these animals, rare endemic-like translocations arise from non-targeted DNA breaks at Myc loci. Deep-sequencing analyses revealed that the deregulated 3' Igh enhancer alpha physically interacts with and remodels 0.45Mb of translocated chromatin. The results thus explain the long-range deregulation of oncogenes in human and mouse B cell tumors.
2013-07-04 | GSE48514 | GEO