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Binding site identification for the Epstein-Barr virus transcription factor Zta in epithelial cells

ABSTRACT: Epstein-Barr virus (EBV) is present in a state of latency in infected memory B-cells and EBV-associated lymphoid and epithelial cancers. Cell stimulation or differentiation of infected B-cells and epithelial cells induces reactivation to the lytic replication cycle. In each cell type, the EBV transcription and replication factor Zta (BZLF1, EB1) plays a role in mediating the lytic cycle of EBV. Zta is a transcription factor that interacts directly with Zta response elements (ZREs) within viral and cellular genomes. Here we undertake chromatin-precipitation coupled to DNA-sequencing (ChIP-Seq) of Zta-associated DNA from cancer-derived epithelial cells. The analysis identified over 14,000 Zta-binding sites in the cellular genome. We assessed the impact of lytic cycle reactivation on changes in gene expression for a panel of Zta-associated cellular genes. Finally, we compared the Zta-binding sites identified in this study with those previously identified in B-cells and reveal substantial conservation in genes associated with Zta-binding sites.

ORGANISM(S): Homo sapiens

PROVIDER: GSE83354 | GEO | 2021/02/20

REPOSITORIES: GEO

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A distinct isoform of lymphoid enhancer binding factor 1 (LEF1) epigenetically restricts EBV reactivation to maintain viral latency

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

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Epstein–Barr virus (EBV) Rta-mediated cell cycle arrest enables permissive replication of EBV and Kaposi’s sarcoma-associated herpesvirus in 293 cells

Project description:Epstein-Barr virus (EBV) Rta is a latent-lytic molecular switch evolutionarily conserved in all gamma-herpesviruses. In previous studies, doxycycline-inducible Rta was shown to potently produce an irreversible G1 arrest followed by cellular senescence in 293 cells. Here, we demonstrate that in this system the inducible Rta not only reactivates resident genome of EBV but also that of Kaposi’s sarcoma-associated herpesvirus (KSHV), to similar efficiency. However, Rta-induced senescence program was terminated by the robust viral lytic cycle replication that eventually caused cell death. Furthermore, prior to the abrupt expression of immediate-early protein (EBV BZLF1 or KSHV RTA), Rta simultaneously down-regulates cell cycle activators (c-Myc, CDK6, CCND2) and up-regulates senescence-related genes (p21, 14-3-3s). Since Rta is a viral immediate-early transcriptional activator, it is envisioned that during the initial stage of viral reactivation, Rta may engage to modulate the host transcriptome, to halt cell cycle progression, and to maintain an ideal environment for manufacturing infectious virions. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE24585: Expression profiling of host genes modulated by Epstein-Barr virus (EBV) Rta in HEK293 cells GSE24586: Expression profiling of host genes modulated by Epstein-Barr virus Rta in nasopharyngeal carcinoma cells

2011-03-31 | E-GEOD-24587 | biostudies-arrayexpress

Interaction between HIV-1 Tat and EBV Zta favours immune escape of B cells by downregulating HLA-ABC expression

Project description:Both Human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) are associated with an increased risk of malignancies. People living with HIV frequently have EBV reactivation and develop EBV-associated B-cell malignancies. In this study, we aimed to uncover the involvement of HIV-1 and EBV co-existence in the development of B-cell malignancies. We studied two viral transcriptional activators (HIV-1 Tat and EBV Zta) and their possible interaction since they both have cell-penetration domains and can be found simultaneously in the blood or cells of people with HIV. We found that Tat and Zta directly bound each other in human B cells, T cells, and blood serum. Using RNA-sequencing, we found that combined Tat and Zta action in B cells differed from a simple combination of two proteins. A subset of genes, activated by Tat or Zta alone, that trigger an immune response and antigen presentation in B cells, remained unchanged when two proteins were combined. B cells, treated or transfected with Tat and Zta, exhibited a substantial decrease in HLA-ABC (MHC class I) expression, a critical component of the antigen processing and presentation pathway. HLA-ABC downregulation induced by Tat and Zta interaction conferred protection against cytotoxic T cell recognition of EBV-infected B cells. Tat and Zta interaction was also observed in serum from an HIV-positive individual. To conclude, we demonstrated for the first time the direct interaction between HIV-1 Tat and EBV Zta; this interaction can bring about immune evasion of EBV-infected or transformed B cells.

2024-04-01 | GSE255092 | GEO

Genomic-scale identification of host genes regulated by EBV during lytic cycle [ChIP-Seq]

Project description:Infection of resting primary B-lymphocytes by Epstein Barr virus (EBV) generates a population of cells that are effectively immortal. This represents the first step in the establishment of life-long viral latency in vivo and generates precursors that can develop into the lymphoid malignancies. However, virus spread requires a switch from latency to the lytic replication cycle, a process orchestrated by the virally encoded protein Zta, an AP1-like transcription factor that interacts with a 7 base-pair DNA sequence element. As Zta has the potential to reprogram the patterns of gene expression in the host cell, we undertook global transcriptome analyses (RNA sequencing) in a Burkitts lymphoma derived cell line in which the Zta is expressed from an inducible promoter, mimicking the switch from latency to lytic cycle. We identified 2,263 host genes whose expression levels were altered. In parallel, we performed chromatin precipitation and next-generation DNA sequencing (ChIP-Seq) to identify genes that are direct targets of Zta. Integrating these data sets revealed 277 host genes that appear to be directly regulated by Zta. Surprisingly, the frequency and distribution of the Zta binding peaks suggests that Zta regulates host genes through long-range enhancers, with a median distance of 25.8kb from the transcriptional start site, rather than equivalents of the promoter elements through which Zta regulates viral genes.

2015-03-18 | GSE58245 | GEO

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