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Proteomics of EBV-infected lytic and refractory cells

ABSTRACT: Most humans are infected with Epstein-Barr virus (EBV), a cancer-causing virus. While EBV generally persists silently in B lymphocytes, periodic lytic (re-)activation of latent virus is central to its life cycle and to most EBV-related diseases. However, a substantial fraction of EBV-infected B cells and tumor cells in a population is refractory to lytic activation. This resistance to lytic activation directly and profoundly impacts viral persistence and effectiveness of oncolytic therapy for EBV+ cancers. To identify the mechanisms that underlie susceptibility to EBV-lytic activation, we used host protein-expression profiling of separated-lytic and -refractory cells.

OTHER RELATED OMICS DATASETS IN: PXD001838PRJNA214314

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Dr Sumita Bhaduri-McIntosh

PROVIDER: MSV000079993 | MassIVE | Fri Jul 22 16:08:00 BST 2016

SECONDARY ACCESSION(S): PXD001838

REPOSITORIES: MassIVE

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Publications

Cellular STAT3 functions via PCBP2 to restrain Epstein-Barr Virus lytic activation in B lymphocytes.

Koganti Siva S Clark Carissa C Zhi Jizu J Li Xiaofan X Chen Emily I EI Chakrabortty Sharmistha S Hill Erik R ER Bhaduri-McIntosh Sumita S

Journal of virology 20150225 9

<h4>Unlabelled</h4>A major hurdle to killing Epstein-Barr virus (EBV)-infected tumor cells using oncolytic therapy is the presence of a substantial fraction of EBV-infected cells that does not support the lytic phase of EBV despite exposure to lytic cycle-promoting agents. To determine the mechanism(s) underlying this refractory state, we developed a strategy to separate lytic from refractory EBV-positive (EBV(+)) cells. By examining the cellular transcriptome in separated cells, we previously d ...[more]

PMID: 25717101

Similar Datasets

Proteomics of EBV-infected lytic and refractory cells

Project description:Most humans are infected with Epstein-Barr virus (EBV), a cancer-causing virus. While EBV generally persists silently in B lymphocytes, periodic lytic (re-)activation of latent virus is central to its life cycle and to most EBV-related diseases. However, a substantial fraction of EBV-infected B cells and tumor cells in a population is refractory to lytic activation. This resistance to lytic activation directly and profoundly impacts viral persistence and effectiveness of oncolytic therapy for EBV+ cancers. To identify the mechanisms that underlie susceptibility to EBV-lytic activation, we used host protein-expression profiling of separated-lytic and -refractory cells.

2016-04-27 | PXD001838 | Pride

Signal Transducer and Activator of Transcription 3 limits Epstein-Barr virus lytic-activation in B lymphocytes.

Project description:We used microarrays to identify genes differentially expressed in EBV-infected human B cells supporting lytic replication vs. those refractory to EBV lytic replication. We used serum from EBV-positive subject (compared to serum from EBV-negative subject) to FACS-separate lytic and refractory cells following treatment of HH514-16 cells with NaB, a lytic cycle inducing agent. RNA from sorted-lytic and sorted-refractory cells were hybridized to microarray.

2013-08-21 | E-GEOD-49568 | biostudies-arrayexpress

Nascent transcriptomics reveal cellular pro-lytic factors upregulated upstream of the latency-to-lytic switch protein of Epstein-Barr virus

Project description:Lytic activation from latency is a key transition point in the life cycle of herpesviruses. Epstein-Barr virus (EBV) is a human herpesvirus that can cause lymphomas, epithelial cancers, and other diseases, most of which require the lytic cycle. While the lytic cycle of EBV can be triggered by chemicals and immunologic ligands, the lytic cascade is only activated when expression of the EBV latency-to-lytic switch protein ZEBRA is turned on. ZEBRA then transcriptionally activates other EBV genes and together with some of those gene products ensures completion of the lytic cycle. However, not every latently-infected cell exposed to a lytic trigger turns expression of ZEBRA on, resulting in responsive and refractory subpopulations. What governs this dichotomy? By examining the nascent transcriptome following exposure to a lytic trigger, we find that several cellular genes are transcriptionally upregulated temporally upstream of ZEBRA. These genes regulate lytic susceptibility to variable degrees in latently-infected cells that respond to mechanistically distinct lytic triggers. While increased expression of these cellular genes defines a pro-lytic state, such upregulation also runs counter to the well-known mechanism of viral nuclease-mediated host shut-off that is activated downstream of ZEBRA. Furthermore, a subset of upregulated cellular genes is transcriptionally repressed downstream of ZEBRA, indicating an additional mode of virus-mediated host shut-off through transcriptional repression. Thus, increased transcription of a set of host genes contributes to a pro-lytic state that allows a subpopulation of cells to support the EBV lytic cycle.

2020-01-13 | GSE141220 | GEO

Signal Transducer and Activator of Transcription 3 limits Epstein-Barr virus lytic-activation in B lymphocytes.

Project description:We used microarrays to identify genes differentially expressed in EBV-infected human B cells supporting lytic replication vs. those refractory to EBV lytic replication.

2013-08-21 | GSE49568 | GEO

The Nucleic Acid Binding Protein SFPQ Represses EBV Lytic Reactivation by Promoting Histone H1 Expression

Project description:Epstein-Barr virus (EBV) uses a biphasic lifecycle of latency and lytic reactivation to infect >95% of adults worldwide. Despite its central role in EBV persistence and oncogenesis, much remains unknown about how EBV latency is maintained. We used a human genome-wide CRISPR/Cas9 screen to identify that the nuclear protein SFPQ was critical for latency. SFPQ supported expression of linker histone H1, which stabilizes nucleosomes and regulates nuclear architecture, but has not been previously implicated in EBV gene regulation. H1 occupied latent EBV genomes, including the immediate early gene BZLF1 promoter. Upon reactivation, SFPQ was sequestered into sub-nuclear puncta, and EBV genomic H1 occupancy diminished. Enforced H1 expression blocked EBV reactivation upon SFPQ knockout, confirming it as necessary downstream of SFPQ. SFPQ knockout triggered reactivation of EBV in B and epithelial cells as well as in Kaposi’s Sarcoma Associated Herpesvirus, suggesting a conserved gamma-herpesvirus role. These findings highlight SFPQ as a major regulator of H1 expression and EBV latency.

2024-04-16 | GSE235265 | GEO

Ceramide Promotes Lytic Reactivation of Epstein-Barr Virus in Gastric Carcinoma

Project description:Epstein-Barr virus (EBV) has a lifelong latency period after initial infection. Rarely, however, when the EBV immediate early gene BZLF1 is expressed by a specific stimulus, the virus switches to the lytic cycle to produce progeny viruses. We found that EBV infection reduced levels of various ceramide species in gastric cancer cells. As ceramide is a bioactive lipid implicated in the infection of various viruses, we assessed the effect of ceramide on the EBV lytic cycle. Treatment with C6-ceramide (C6-Cer) induced an increase in the endogenous ceramide pool and increased production of the viral product as well as BZLF1 expression. Treatment with the ceramidase inhibitor ceranib-2 induced EBV lytic replication with an increase in the endogenous ceramide pool. The glucosylceramide synthase inhibitor Genz-123346 inhibited C6-Cer-induced lytic replication. C6-Cer induced ERK1/2 and CREB phosphorylation, c-JUN expression, and accumulation of the autophagosome marker LC3B. Treatment with MEK1/2 inhibitor U0126 or autophagy initiation inhibitor 3-MA suppressed C6-Cer-induced EBV lytic replication. In contrast, the autophagosome-lysosome fusion inhibitor chloroquine induced BZLF1 expression. Transfection with siCREB reduced ERK1/2 phosphorylation and C6-Cer-induced BZLF1 expression. On the other hand, siJUN transfection did not affect BZLF1 expression. Our results show that increased endogenous ceramide and glycosyl ceramide (GlyCer) following C6-Cer treatment induce EBV lytic replication in gastric cancer cells via ERK1/2 and CREB phosphorylation and autophagosome accumulation.

2023-12-20 | MTBLS7649 | MetaboLights

Effect of Effect of lytic replication on EBV and cell gene expression

Project description:The effect of Epstein Barr virus replication on cellular gene expression was studied using AGSiZ epithelial cells which are derived from a gastric carcinoma. The cell line is infected with a recombinant strain of EBV known as Akata BX-1. The cell line was further stably transduced with an inducible EBV Zta transactivator gene. When cells are treated with doxycycline, robust lytic replication of EBV is achieved. Cells made permissive for lytic replication in this manner were harvested for RNA suitable for deep sequencing at 24 and 48 hours post induction in parallel with cells that were mock induced with doxycycline to serve as a control for cells not undergoing EBV replication.

2021-04-15 | GSE155811 | GEO

BET proteins bind the lytic origins of replication [MutuI ChIP-seq]

Project description:Lytic infection by the Epstein-Barr virus (EBV) poses numerous health risks, such as infectious mononucleosis and lymphoproliferative disorder. We demonstrate that JQ1 and other BET inhibitors block two different steps in the sequential cascade of the EBV life cycle: expression of the immediate-early gene BZLF1 and lytic genome replication. This represents a novel mode of action for antiviral drugs that may increase efficacy and decrease emergence of resistance. The ChIP-seq data below show that the BET proteins bind to both EBV lytic origins of replication.

2017-06-30 | GSE84213 | GEO

EBNA1 ChIP-seq and MNase-seq in EBV-positive MUTU cell lines

Project description:Epstein-Barr Virus (EBV), which is associated with multiple human tumors, persists as a minichromosome in the nucleus of B-lymphocytes and induces malignancies through incompletely understood mechanisms. Here, we present a large-scale functional genomic analysis of EBV. Our experimentally generated nucleosome positioning maps and viral protein binding data were integrated with over 700 publicly available high-throughput sequencing data sets for human lymphoblastoid cell lines mapped to the EBV genome. We found that viral lytic genes are coexpressed with cellular cancer-associated pathways, suggesting that the lytic cycle may play an unexpected role in virus-mediated oncogenesis. Host regulators of viral oncogene expression and chromosome structure were identified and validated, revealing a role for the B-cell-specific protein Pax5 in viral gene regulation and the cohesin complex in regulating higher order chromatin structure. Our findings provide a deeper understanding of latent viral persistence in oncogenesis and establish a valuable viral genomics resource for future exploration. Six sequencing experiments were performed. One EBNA1 ChIP-seq was controlled with IgG ChIP-seq. Two MNase-seq biological replicates were each conrolled by input seq using the same cells subjected to MNase digestion.

2012-08-28 | E-GEOD-39913 | biostudies-arrayexpress

JQ1 prevents BRD4 recruitment to the lytic origins of replication [Akata-Zta DNA-seq]

2017-06-30 | GSE98772 | GEO

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