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The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): human gammaherpesvirus 4 Homo sapiens

PROVIDER: GSE239995 | GEO | 2023/10/11

REPOSITORIES: GEO

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The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [HiChIP]

Project description:Epstein-Barr virus (EBV) establishes lifelong asymptomatic infection by replication of its chromatinized episomes with the host genome. EBV exhibits different latency-associated transcriptional repertoires, each with distinct three-dimensional structures. CTCF, Cohesin and PARP1 are involved in maintaining viral latency and establishing episome architecture. Epstein-Barr virus-associated gastric cancer (EBVaGC) represents 1.3% to 30.9% of all gastric cancers globally. EBV-positive gastric cancers exhibit an intermediate viral transcription profile known as "Latency II", expressing specific viral genes and noncoding RNAs. In this study, we investigated the impact of PARP1 inhibition on CTCF/Cohesin binding in Type II latency. We observed destabilization of the binding of both factors, leading to a disrupted three-dimensional architecture of the episomes and an altered viral gene expression. Despite sharing the same CTCF binding profile, Type I, II, and III latencies exhibit different 3D structures that correlate with variations in viral gene expression. Additionally, our analysis of H3K27ac-enriched interactions revealed differences between Type II latency episomes and a link to cellular transformation through docking of the EBV genome at specific sites of the Human genome, thus promoting oncogene expression. Overall, this work provides insights into the role of PARP1 in maintaining active latency and novel mechanisms of EBV-induced cellular transformation.

2023-10-11 | GSE239992 | GEO

The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [HiC]

2023-10-11 | GSE239989 | GEO

The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [RNA-seq]

2023-10-11 | GSE239994 | GEO

The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [ChIP-seq]

2023-10-11 | GSE239987 | GEO

The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC

Project description:The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC

| PRJNA1001883 | ENA

The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [HiChIP]

Project description:The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [HiChIP]

| PRJNA1001891 | ENA

The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [HiC]

Project description:The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [HiC]

| PRJNA1001888 | ENA

The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [RNA-seq]

Project description:The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [RNA-seq]

| PRJNA1001894 | ENA

The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [ChIP-seq]

Project description:The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [ChIP-seq]

| PRJNA1001873 | ENA

Genome-wide analysis of Epstein-Barr virus (EBV) isolated from EBV-associated gastric carcinoma (EBVaGC).

Project description:Epstein-Barr virus (EBV) is linked to the development of a variety of malignancies, including EBV-associated gastric carcinoma (EBVaGC). In this study, EBVaGC was detected in 15 (7.3%) of 206 GC cases. To identify the EBV genomic variation, EBV genomic sequences isolated from 9 EBVaGC biopsy specimens were successfully retrieved, designated EBVaGC1 to EBVaGC9. By comparative analysis of these strains with another 6 completely sequenced EBV strains, EBV-wild type, B95-8, AG876, GD1, GD2, and HKNPC1, it was demonstrated that EBVaGC1 to 9 were most closely related to the GD1 strain. Phylogenetic analysis of the GC biopsy specimen-derived EBV (GC-EBV) genomes was subsequently performed to assess their genomic diversity and it exhibited the greatest divergence from the type 2 strain, AG876. Compared with the reference EBV strain GD1, they harbored 961 variations in total, including 919 substitutions, 23 insertions, and 19 deletions. Single nucleotide polymorphism (SNP) density varied substantially across all known open reading frames and was highest in latency-associated genes. Moreover, we identified 2 interstrain recombinants at the EBNA1 locus, which provided a further mechanism for the generation of diversity. Some T-cell epitope sequences in EBNA1 and LMP2A genes showed extensive variation across strains, which implied their importance in the development of vaccines and T-cell therapy. In conclusion, we reported the first genome-wide view of sequence variation of EBV isolated from primary EBVaGC biopsy specimens, which might serve as an effective method for further understanding the genomic variations contribute to EBVaGC carcinogenesis and treatment.

| S-EPMC4826252 | biostudies-literature

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