Expression data from EBV-encoded latent membrane protein 2A (LMP2A) positive and negative nasopharyngeal carcinoma (NPC) cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE118807 | GEO | 2018/08/21
REPOSITORIES: GEO
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Project description:Expression data from EBV-encoded latent membrane protein 2A (LMP2A) positive and negative nasopharyngeal carcinoma (NPC) cell lines
| PRJNA486838 | ENA
Project description:Survival of all B cells depends on signals from the B-cell receptor (BCR). In BCRnegative B cells the latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) replaces this survival signal and might play a role in the development of EBV-positive Hodgkin lymphomas and posttransplantation lymphoproliferative disease. In these BCR-negative cells LMP2A provides a ‘tonic’ signal similar to BCR’s constitutive expression in the absence of antigen in order to maintain activating signaling pathways common to both receptor molecules. In most latently EBV-infected B cells LMP2A and BCR are co-expressed but it is largely unclear what LMP2A contributes with respect to B-cell activation, proliferation and viral latency in these BCR-positive cells. A common model suggests that LMP2A maintains herpesviral latency by blocking BCR-mediated signals but how LMP2A could serve both antithetical ends in BCRnegative and BCR-positive cells is elusive. Our comparative analysis of BCR and LMP2A now indicates that LMP2A is a true BCR mimic that dominates BCR-operated signaling pathways in EBV-infected, BCR-positive cells to provide activation signals, support stable infections in vivo and allow exit from latency. These findings suggest that LMP2A co-opts the situation in anergic B cells, where continuous BCR signaling results in maintenance of the anergic state accompanied by unresponsiveness to acute BCR stimulation. The microarray experiment was used to compare effects of BCR and LMP2A on gene expression regulation. EBV's LMP2A and the human BCR activate similar cellular target genes; some genes are regulated solely by BCR or LMP2A, no gene is counter regulated A 12 chip study using cDNA from three separate 2525 LMP2A knockout LCL cultures and three separate 3696.10 LMP2A:mCD69 LCL cultures; each culture tested before and after 90 min stimulation of the BCR and LMP2A:mCD69, respectively.
2011-01-01 | E-GEOD-25434 | biostudies-arrayexpress
Project description:Survival of all B cells depends on signals from the B-cell receptor (BCR). In BCRnegative B cells the latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) replaces this survival signal and might play a role in the development of EBV-positive Hodgkin lymphomas and posttransplantation lymphoproliferative disease. In these BCR-negative cells LMP2A provides a ‘tonic’ signal similar to BCR’s constitutive expression in the absence of antigen in order to maintain activating signaling pathways common to both receptor molecules. In most latently EBV-infected B cells LMP2A and BCR are co-expressed but it is largely unclear what LMP2A contributes with respect to B-cell activation, proliferation and viral latency in these BCR-positive cells. A common model suggests that LMP2A maintains herpesviral latency by blocking BCR-mediated signals but how LMP2A could serve both antithetical ends in BCRnegative and BCR-positive cells is elusive. Our comparative analysis of BCR and LMP2A now indicates that LMP2A is a true BCR mimic that dominates BCR-operated signaling pathways in EBV-infected, BCR-positive cells to provide activation signals, support stable infections in vivo and allow exit from latency. These findings suggest that LMP2A co-opts the situation in anergic B cells, where continuous BCR signaling results in maintenance of the anergic state accompanied by unresponsiveness to acute BCR stimulation. The microarray experiment was used to compare effects of BCR and LMP2A on gene expression regulation. EBV's LMP2A and the human BCR activate similar cellular target genes; some genes are regulated solely by BCR or LMP2A, no gene is counter regulated
2011-01-01 | GSE25434 | GEO
Project description:Abstract: Epstein-Barr virus (EBV) infects germinal center (GC) B cells and establishes persistent infection in memory B cells. EBV-infected B cells sometimes cause B cell malignancies in humans with T- or NK-cell deficiency. We now find EBV-encoded Latent Membrane Protein 2A (LMP2A) to mimic B cell antigen receptor (BCR) signaling in murine GC B cells, causing altered humoral immune responses and autoimmune diseases. Investigation of the impact of LMP2A on B cell differentiation in mice that conditionally express LMP2A in GC B cells, or all B-lineage cells, found LMP2A expression enhanced not only BCR signals but also plasma-cell differentiation, in vitro and in vivo. Conditional LMP2A expression in GC B cells resulted in preferential selection of low-affinity antibody–producing B-cells despite apparently normal GC formation. GC B cell-specific LMP2A expression led to systemic lupus erythematosus-like autoimmune phenotypes in an age-dependent manner. Epigenetic profiling of LMP2A B cells found increased H3K27ac and H3K4me1 signals at the Zbtb20 locus. We conclude that LMP2A reduces the stringency of GC B cell selection and may contribute to persistent EBV infection and pathogenesis by providing GC B cells with pro-survival signals. Significance Statement: Epstein-Barr virus (EBV) is a human herpesvirus that establishes persistent infection of the B-cell compartment. EBV is associated with autoimmune diseases, including systemic lupus erythematosus (SLE). However, the molecular mechanisms by which EBV contributes to autoimmunity remain unclear. We used transgenic mouse models to study the role of EBV-encoded Latent membrane protein 2A (LMP2A), which mimics B-cell receptor signaling. Interestingly, LMP2A not only enhanced B-cell survival, but also upregulated the transcription factor Zbtb20 and promoted plasma cell differentiation. When expressed late in B-cell development, LMP2A also caused prominent features of SLE, including autoantibody production with kidney immune complex deposition. Our findings suggest that LMP2A has important roles in B cell activation, differentiation and the development of EBV-associated autoimmune diseases.
2015-10-01 | GSE71408 | GEO
Project description:Epstein-Barr virus (EBV) infects human B cells and reprograms them to allow virus replication and persistence. One key viral factor in this process is latent membrane protein 2A (LMP2A), which has been described as a B cell receptor (BCR) mimic promoting malignant transformation. However, how LMP2A signaling contributes to tumorigenesis remains elusive. By systematically comparing LMP2A and BCR signaling using quantitative phosphoproteomics and transcriptome profiling, we identified molecular mechanisms through which LMP2A affects B cell biology. Consistent with previous literature, we found that LMP2A mimics a subset of BCR signaling events, including tyrosine-phosphorylation of the kinase SYK, the calcium initiation complex consisting of BLNK, BTK, PLC2, and its downstream transcription factor NFAT. However, the vast majority of LMP2A-induced signaling events markedly differed from those induced by BCR stimulation. These included differential phosphorylation of kinases, phosphatases, adaptor proteins, transcription factors such as NFB and TCF3, as well as widespread changes in the transcriptional output of LMP2A-expressing B cells. LMP2A affected apoptosis and cell cycle checkpoints by dysregulating the expression of apoptosis regulators such as Bcl-xL and the tumor suppressor retinoblastoma-associated protein (RB1). Accordingly, LMP2A cooperated with drivers of Burkitt lymphoma, overexpressed MYC and an oncogenic cyclin D3 mutant, by counteracting the pro-apoptotic effects of MYC and by further inhibiting RB1 function to promote cell growth. Our results indicate that LMP2A rewires rather than mimics BCR signaling, promoting a signaling output that predisposes EBV-infected B cells to hyperproliferation and eventual malignant transformation.
2020-09-22 | PXD018566 | Pride
Project description:Nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia and southern China. The primary treatment for NPC is radiotherapy. Despite of the encouraging results of radiotherapy, local recurrence or distant metastases of NPC after the initial therapy is frequently found due to radioresistance. Therefore, there is an urgent need to identify genes that control radiosensitivty, aiming to reduce disease recurrence. Epstein-Barr virus (EBV) infection was closely associated with undifferentiated NPC. EBV-encoded microRNAs (miRNAs) played crucial roles in the pathogenesis of NPC. Ebv-miR-BART7 belongs to the 44 EBV BART miRNAs and was found to be up-regulated in NPC tissues and plasma. Forced expression of ebv-miR-BART7 enhanced the radiosensitivity of NPC cells. However, the mechanisms underlying the sensitizing effect of ebv-miR-BART7 on radiation remain largely unknown. Given that miRNA exerts biological functions by regulating its targets, we used microarray to identify the targets of ebv-miR-BART7 that regulate radiosensitivity of NPC cells.
2017-03-31 | GSE79571 | GEO
Project description:Gene expression profile of splenic B cells (CD19+) from transgenic mice expressing the Epstein-Barr virus (EBV) latent membrane proteins (LMP) 1 and/or LMP2A. Freshly harvested primary B cells were profiled. B lymphocytes from transgenic LMP1, LMP2A, LMP1/2A mice and negative littermates were profiled from 6 month old adult mice; lymphoma cells were passaged in SCID mice and profiled for three LMP1 positive lymphomas and one negative lymphoma.
2012-09-01 | GSE38954 | GEO
Project description:Comprehensive Profiling of Epstein-Barr Virus-Encoded miRNAome Associated with Specific Latent Type in Tumor Cells Epstein-Barr virus (EBV) is an etiological cause of many human lymphocytic and epithelial malignancies. EBV expressed different genes associated with three latent types. So far as many as 44 EBV-encoded miRNA species have been found but their comprehensive and comparative profiling is not well documented in three latent infection states linked to various tumor cells. In this study, we utilized the polyA-tailed quantitative real time RT-PCR procedure to measure the relative abundance of viral miRNA species that linked to individual viral genome locations in combination with microarray evaluation in a subset of representative lymphoid and epithelial tumor cells undergoing various types of EBV latent infection. The results showed that miR-BHRF1 family and miR-BART family are expressed differentially in a tissue-dependent and latency-dependent manner. In particular, in NPC tissue and the only EBV consistently harboring cell line C666-1 with latency type II, there were highly abundant miR-BART family but not miR-BHRF1 family members that accounted for more than 10% of the whole known human miRNA library, implicating their important roles in maintaining EBV latent infection and driving NPC tumorigenesis. In addition, EBV miRNAome-based clustering analysis could classify three distinct EBV latency types, meanwhile, for the first time, we found and subsequently evaluated a novel secret latent switch in BL cell line Daudi from type I to III, which was unable to be identified by traditional latent biomarkers. Together, our data provided an in-depth and comparative profiling of EBV miRNA transcriptome in correspondence with three EBV latent infections, suggesting that different viral miRNA species were involved in divergent host cell carcinogenesis. Finally, EBV miRNAome, as a cluster of novel latency biomarkers expressed variedly in tumor cells, greatly complements and improves the classical typing criteria in conjunction with other latently expressed marker genes. 2 NPC tissue samples and 2 NPC cell lines and 5 lymphocytic cell lines
2012-07-06 | E-GEOD-33225 | biostudies-arrayexpress
Project description:Gene expression profile of splenic B cells (CD19+) from transgenic mice expressing the Epstein-Barr virus (EBV) latent membrane proteins (LMP) 1 and/or LMP2A. Freshly harvested primary B cells were profiled. B lymphocytes from transgenic LMP1, LMP2A, LMP1/2A mice and negative littermates were profiled from 6 month old adult mice; lymphoma cells were passaged in SCID mice and profiled for three LMP1 positive lymphomas and one negative lymphoma. 12 total samples. 4 transgenic B lymphocyte samples pooled from multiple biological replicates were hybridized to duplicate microarrays: LMP1 (pooled from 2 replicates), LMP2A (pooled from 3 replicates); LMP1/2A (pooled from 5 replicates), negative littermates (pooled from 4 replicates). 3 biological replicates of LMP1 lymphomas expressing high, medium and low levels of LMP1 and; 1 negative lymphoma was hybridized to 1 microarray chip. The reference sample consisted of 4 biological replicates of splenic B cells (CD19+) pooled from 4-7 month old non-transgenic Balb/c mice. The same reference was used for all hybridizations.
2012-09-01 | E-GEOD-38954 | biostudies-arrayexpress
Project description:Extracellular vesicles (EV) mediate intercellular communication events and alterations in normal vesicle content contribute to function and disease initiation or progression. The ability to package a variety of cargo and transmit molecular information between cells renders EVs important mediators of cell to cell crosstalk. Latent membrane protein 1 (LMP1) is a chief viral oncoprotein expressed in most Epstein-Barr virus (EBV)-associated cancers and is released from cells at high levels in EVs. LMP1 containing EVs have been demonstrated to promote cell growth, migration, differentiation, and regulate immune cell function. Despite these significant changes in recipient cells induced by LMP1 modified EVs, the mechanism how this viral oncogene modulates the recipient cells towards these phenotypes is not well understood. We hypothesize that LMP1 alters EV content and following uptake of the LMP1-modified EVs by the recipient cells results in the activation of cell signaling pathways and increased gene expression which modulates the biological properties of recipient cell towards a new phenotype. Our results show that LMP1 expression alters the EV protein and microRNA content packaged into EVs.
2020-11-03 | PXD021914 | Pride