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Gene expression profiles of epithelial cells infected with microRNA-negative and -positive Epstein-Barr viruses

ABSTRACT: The Epstein-Barr virus (EBV) encodes its own microRNAs (miRNAs); however, their biological roles remain elusive. The commonly used EBV B95-8 strain lacks a 12 kb genomic region, known as BamHI A Rightward Transcripts (BART) locus, which encodes a number of viral miRNAs (BART miRNAs). These miRNAs are expressed abundantly in EBV-positive epithelial malignancies, suggesting that the 12 kb region somehow contributes to EBV-mediated epithelial carcinogenesis. Bacterial artificial chromosome (BAC) technology was used to generate an EBV B95-8 strain in which the 12 kb region was fully restored at its native locus (BART-restored virus). HEK293 and AdAH cells infected with either the parental BART-deleted virus or the BART-restored virus were established. The gene expression profiles of these cells were examined to identify cellular target genes of BART miRNAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE58723 | GEO | 2015/02/05

SECONDARY ACCESSION(S): PRJNA253273

REPOSITORIES: GEO

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Gene expression profiles of epithelial cells infected with microRNA-negative and -positive Epstein-Barr viruses

Project description:The Epstein-Barr virus (EBV) encodes its own microRNAs (miRNAs); however, their biological roles remain elusive. The commonly used EBV B95-8 strain lacks a 12 kb genomic region, known as BamHI A Rightward Transcripts (BART) locus, which encodes a number of viral miRNAs (BART miRNAs). These miRNAs are expressed abundantly in EBV-positive epithelial malignancies, suggesting that the 12 kb region somehow contributes to EBV-mediated epithelial carcinogenesis. Bacterial artificial chromosome (BAC) technology was used to generate an EBV B95-8 strain in which the 12 kb region was fully restored at its native locus (BART-restored virus). HEK293 and AdAH cells infected with either the parental BART-deleted virus or the BART-restored virus were established. The gene expression profiles of these cells were examined to identify cellular target genes of BART miRNAs. Total RNAs of 2 independent v-miRNA-positive HEK293 (or AdAH) cells and 2 independent v-miRNA-negative cells HEK293 (or AdAH) cells were processed for Microarray analysis using 3D-Gene human Oligo chip 25k (Toray, Tokyo, Japan).

2015-02-05 | E-GEOD-58723 | biostudies-arrayexpress

Circular DNA tumor viruses make circular RNAs

Project description:Epstein-Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV) cause ~2% of all human cancers. RNase R-resistant RNA sequencing revealed that both gammaherpesviruses encode multiple, uniquely stable, circular RNAs (circRNA). EBV abundantly expressed both exon-only and exon-intron circRNAs from the BART locus (circBARTs) formed from a spliced BART transcript and excluding the EBV miRNA region. CircBARTs were expressed in all verified EBV latency types, including EBV- positive post-transplant lymphoproliferative disease (PTLD), Burkitt lymphoma, nasopharyngeal carcinoma, and AIDS-associated lymphoma tissues and cell lines. Only cells infected with the B95-8 EBV strain, with a 12-kb BART locus deletion, were negative for EBV circBARTs. Less abundant levels of EBV circRNAs originating from LMP2 and BHLF1-encoding genes were also identified. CircRNA sequencing of KSHV- infected PEL cells revealed a KSHV-encoded circRNA from the vIRF4 locus (circvIRF4) that was constitutively expressed. In addition, KSHV polyadenylated nuclear (PAN) RNA locus generated a swarm (>100) of multiply backspliced, low-abundance RNase R- resistant circRNAs originating in both sense and antisense directions consistent with a novel hyper-backsplicing mechanism. In EBV and KSHV co-infected cells, exon-only EBV circBARTS were located more in the cytoplasm, whereas the intron-retaining circBARTs were found in the nuclear fraction. KSHV circvIRF4 and circPANs were detected in both nuclear and cytoplasmic fractions. Among viral circRNAs tested, none were found in polysome fractions from KSHV-EBV co-infected BC1 cells although low abundance protein translation from viral circRNAs could not be excluded. CircRNAs are a new class of viral transcripts expressed in gammaherpesvirus-related tumors that might contribute to viral oncogenesis.

2018-07-28 | GSE117798 | GEO

The forced loss of Epstein Barr virus from Burkitt's lymphoma cells: uncomplemented cells vs BART miRNA complemented cells.

Project description:Transcriptional profiling of Burkitt lymphoma cells engineered to inducibly express dominant negative EBNA1 (dnEBNA1), which forces the loss of Epstein Barr virus (EBV). Profiles are made of cells in which all of EBV is lost (dnEBNA1 on) or all of EBV except the BART miRNAs is lost (dnEBNA1 on, BART miRNAs ectopically expressed). This is a 2-condition experiment: uncomplemented cells (EBV evicted with dnEBNA1), and BART-complemented cells (EBV evicted with dnEBNA1, BART miRNAs expressed ectopically). There are 3 biological replicates for each condition.

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Expression of EBV miRNAs in numerous EBV-positive cell lines

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The forced loss of Epstein Barr virus from Burkitt's lymphoma cells: uncomplemented cells vs BART miRNA complemented cells.

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miRNA-Seq profiling of nasopharyngeal carcinoma (NPC) and normal control samples

Project description:Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with nasopharyngeal carcinoma (NPC). EBV encodes two groups of microRNAs (miRNAs) which are divided into BamHI fragment H rightward open reading frame 1 (BHRF1) and BamHI-A rightward transcripts (BART) microRNAs. EBV miR-BARTs have been found to be involved in the development and progression of NPC. However, the role of EBV-miR-BARTs in NPC progression remains illusive. This study aimed to investigate the role of EBV-miR-BARTs in NPC and explore the underlying mechanisms.

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Identification of novel Epstein-Barr Virus miRNA genes from Nasopharyngeal Carcinomas

Project description:MicroRNAs (miRNAs) represent a conserved class of small non-coding RNAs that are found in all higher eukaryotes as well as some DNA viruses. MiRNAs are 20-25 nucleotides (nt) in length and have important regulatory functions in biological processes such as embryonic development, cell differentiation, hormone secretion or metabolism. Furthermore, miRNAs have been implicated in the pathology of various diseases including cancer. MiRNA expression profiles not only classify different types of cancer but also may even help to characterize distinct tumor stages, therefore constituting a valuable tool for prognosis. Here we report the miRNA profile of Epstein-Barr Virus (EBV)-positive nasopharyngeal carcinoma (NPC) tissue samples characterized by cloning and sequencing. We find that all EBV miRNAs from the BART region are expressed in NPC tissues whereas ebv-miRNAs from the BHRF1 region are not found. Moreover, we identify two novel EBV miRNA genes originating from the BART region that have not been found in other tissues or cell lines before. We also identify three new human miRNAs, which might be specific for nasopharyngeal tissues. We further show that a number of different cellular miRNAs are upor down-regulated in NPC tissues compared to control tissue including miR-15a and miR-16. We find that the tumor suppressor BRCA-1 is a target of miR-15a as well as miR-16 suggesting a miRNA role in NPC pathogenesis. 2 pairs of NPC and control tissues from 2 patients (4 samples in total) were examined.

2009-02-07 | E-GEOD-14738 | biostudies-arrayexpress

Expression of EBV miRNAs in numerous EBV-positive cell lines

Project description:EBV-positive cell lines were assayed for expression of EBV miRNAs. The names of the miRNAs are from miRBase from Fall 2007. Microarray probes are tandem complements of the mature miRNA sequence. We assayed Burkitt's lymphoma (BL), Nasopharyngeal carcinoma, post-transplant lymphoproliferative disease (PTLD), primary effusion lymphoma, and lymphoblastoid cell lines. We also assayed primary B cells that were infected with the B95-8 strain of EBV, which was found to express EBV miRNAs as early as 20 hours post infection. We have found PTLD and BLs from HIV-positive donors both express EBV miRNAs. These types of cell lines have not previously been found to express viral miRNAs. We have found that cells that support type I and type II latency express only the BART miRNAs, whereas cells that support type III latency express BART and BHRF1 miRNAs. Furthermore, BL cell lines that spontaneously lose EBV express levels of the viral miRNAs that are at least 5-fold lower than cell lines that do not lose EBV. In total, 48 samples have been assayed and included in this study. EBV-negative control samples are not included in this data set, but raw and processed data may be requested from the contributors. These EBV-negative cell lines include the Burkitt's lymphoma cell lines, BJAB and Akata-negative, the gastric carcinoma cell line, AGS, and uninfected primary B cells. Of the 48 samples, we have assayed 22 different EBV-positive cell lines and 4 different time points after infection of primary B cells with EBV. Replicates of the majority of cell lines is included in this data set. Replicates are from independent RNA isolations that were then hybridized to individual microarrays.

2008-11-30 | E-GEOD-12014 | biostudies-arrayexpress

Identification of novel Epstein-Barr Virus miRNA genes from Nasopharyngeal Carcinomas

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Expression data of EBV-positive and EBV-negative subclones of gastric adenocarcinoma cell line AGS

Project description:Gastric cancer is one of the most common cancers worldwide. Epstein-Barr virus-associated gastric cancer accounts for approximately 10% of all gastric cancers. EBV expresses its own proteins and miRNAs (BART miRNAs) and regulates host gene expression. In this study, we examined the effect of EBV infection on host mRNA expression. Differential gene expression was analyzed between EBV-negative human gastric cancer cell line AGS and EBV-positive human gastric cancer cell line AGS-EBV.

2019-10-14 | GSE135644 | GEO

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