Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Epstein-Barr virus encodes at least 44 microRNAs that are grouped in two clusters located around the BHRF1 gene and within the BART transcript. The expression pattern of these microRNAs both depends on the lineage of the infected cells and on the type of viral latency. Whilst BART microRNAs are expressed in all EBV-infected tumors, the BHRF1 locus is nearly exclusively expressed in cells that display a type III latency. However, the BART microRNA expression level is several orders of magnitude higher in epithelial cells than in B cells. Genetic studies have demonstrated that the BHRF1 microRNA cluster enhances the initial phases of primary B cell transformation through inhibition of apoptosis. A similar role has been ascribed to the BART microRNAs although their contribution to this process seems more limited. These microRNAs also enhance the survival of B cell lymphoma cells. Using various strategies including high throughput assays, several groups have identified mRNAs targeted by the EBV microRNAs. Here we compare the results of the published high throughput screens and review the viral and cellular genes thought to represent high confidence targets for the EBV microRNAs. Although genetic studies allow unequivocal evaluation of the functions served by the microRNAs, only a few key targets have been identified so far.
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PMID:Genetics of Epstein-Barr virus microRNAs. 2460 23

Primary central nervous system (pCNS) posttransplant lymphoproliferative disorder (PTLD) is a complication of solid organ transplantation characterized by poor outcome. In contrast to systemic PTLD, Epstein-Barr virus (EBV)-association of pCNS PTLD is almost universal, yet viral and cellular data are limited. To identify differences in the pattern of EBV-association of pCNS and systemic PTLD, we analyzed the expression of latent and lytic EBV transcripts and the viral and cellular microRNAome in nine pCNS (eight EBV-associated) and in 16 systemic PTLD samples (eight EBV-associated). Notably although 15/16 EBV-associated samples exhibited a viral type III latency pattern, lytic transcripts were also strongly expressed. Members of the ebv-miR-BHRF1 and ebv-miR-BART clusters were expressed in virtually all EBV-associated PTLD samples. There were 28 cellular microRNAs differentially expressed between systemic and pCNS PTLD. pCNS PTLD expressed lower hsa-miR-199a-5p/3p and hsa-miR-143/145 (implicated in nuclear factor kappa beta and c-myc signaling) as compared to systemic PTLD. Unsupervised nonhierarchical clustering of the viral and cellular microRNAome distinguished non-EBV-associated from EBV-associated samples and identified a separate group of EBV-associated pCNS PTLD that displayed reduced levels of B cell lymphoma associated oncomiRs such as hsa-miR-155, -21, -221 and the hsa-miR-17-92 cluster. EBV has a major impact on viral and cellular microRNA expression in EBV-associated pCNS PTLD.
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PMID:A comprehensive analysis of the cellular and EBV-specific microRNAome in primary CNS PTLD identifies different patterns among EBV-associated tumors. 2513 Feb 12

Epstein-Barr virus (EBV) encodes 49 microRNAs (miRNAs) in the BART and BHRF1 regions of its genome. Although expression profiles of EBV-encoded miRNAs have been reported for EBV-positive cell lines and nasopharyngeal carcinoma, to date there is little information about total miRNA expression, including cellular and viral miRNAs, in the primary tumors of EBV-associated B-lymphoproliferative disorders. In this study, next-generation sequencing and quantitative real-time reverse transcription-PCR were used to determine the expression profiles of miRNAs in EBV-infected cell lines and EBV-associated B-cell lymphomas, including AIDS-related diffuse large B-cell lymphoma (DLBCL), pyothorax-associated lymphoma, methotrexate-associated lymphoproliferative disorder, EBV-positive DLBCL of the elderly, and Hodgkin lymphoma. Next-generation sequencing revealed that EBV-encoded miRNAs accounted for up to 34% of total annotated miRNAs in these cases. Expression of three miR-BHRF1s was significantly higher in AIDS-related DLBCL and pyothorax-associated lymphoma compared with methotrexate-associated lymphoproliferative disorder and EBV-positive DLBCL of the elderly, suggesting the association of miR-BHRF1s expression with latency III EBV infection. Heat map/clustering analysis of expression of all miRNAs, including cellular and EBV miRNAs, by next-generation sequencing demonstrated that each EBV tumor, except methotrexate-associated lymphoproliferative disorder, formed an isolated cluster. Principal component analysis based on the EBV-encoded miRNA expression showed that each EBV tumor formed a distinguished cluster, but AIDS-related DLBCL and pyothorax-associated lymphoma formed larger clusters than other tumors. These data suggest that expression of miRNAs, including EBV-encoded miRNAs, is associated with the tumor type and status of virus infection in these tumors.
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PMID:Next-generation sequencing of miRNAs in clinical samples of Epstein-Barr virus-associated B-cell lymphomas. 2818 23

One hundred thirty-eight new Epstein-Barr virus (EBV) genome sequences have been determined. One hundred twenty-five of these and 116 from previous reports were combined to produce a multiple-sequence alignment of 241 EBV genomes, which we have used to analyze variation within the viral genome. The type 1/type 2 classification of EBV remains the major form of variation and is defined mostly by EBNA2 and EBNA3, but the type 2 single-nucleotide polymorphisms (SNPs) at the EBNA3 locus extend into the adjacent gp350 and gp42 genes, whose products mediate infection of B cells by EBV. A small insertion within the BART microRNA region of the genome was present in 21 EBV strains. EBV from saliva of U.S. patients with chronic active EBV infection aligned with the wild-type EBV genome with no evidence of WZhet rearrangements. The V3 polymorphism in the Zp promoter for BZLF1 was found to be frequent in nasopharyngeal carcinoma cases from both Hong Kong and Indonesia. Codon usage was found to differ between latent and lytic cycle EBV genes, and the main forms of variation of the EBNA1 protein have been identified.IMPORTANCE Epstein-Barr virus causes most cases of infectious mononucleosis and posttransplant lymphoproliferative disease. It contributes to several types of cancer, including Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. EBV genome variation is important because some of the diseases associated with EBV have very different incidences in different populations and geographic regions, and differences in the EBV genome might contribute to these diseases. Some specific EBV genome alterations that appear to be significant in EBV-associated cancers are already known, and current efforts to make an EBV vaccine and antiviral drugs should also take account of sequence differences in the proteins used as targets.
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PMID:Sequence Variation of Epstein-Barr Virus: Viral Types, Geography, Codon Usage, and Diseases. 3011 70