Ebv is a gammaherpesvirus of the lymphocryptovirus lcv genus and is closely related to other lcvs present in old world nonhuman primates, including ebvlike viruses of chimpanzees and rhesus monkeys. Epsteinbarr virus ebv infects more than 90% of the adult population worldwide at some point in their lives, usually with no ill e ects 1. Epsteinbarr virus ebv is a human herpesvirus implicated in cancer and autoimmune disorders. Probing its possible chromatin localization by chart revealed eber2s presence at the terminal repeats trs of the latent ebv genome, overlapping previously identified binding sites for the b cell transcription factor pax5. Ebv gene expression and regulation request pdf researchgate. Epsteinbarr virus is known to cause nasopharyngeal carcinoma. Epsteinbarr virus and autoimmune diseases national. Determination and genomewide analysis of epsteinbarr virus ebv. An atlas of the epsteinbarr virus transcriptome and. Ebv share similar sequences and genetic organization, and they maintain persistent infection in the oropharynx and in b cells. After updating the annotation of the genome, 23 open reading frames were chosen for expression in escherichia coli, initially selecting. Dx ebv assay 96 37021 direct quantitative detection of.
The aim of this prospective study was to evaluate the relationship between viral epstein. Epsteinbarr virus ebv, also known as human herpesvirus 4, is a member of the herpes virus family. The human nuclear genome is a highly complex arrangement of two sets of 23 chromosomes, or dna molecules. Early ebv genomic diversity and convergence towards the b95. Research paper genomewide analysis of epsteinbarr virus. Progress and problems in understanding and managing. Ebv2 transforms b cells less efficiently than ebv1in vitro, and the viability of ebv2 lymphoblastoid cell lines is less than that of. The prognostic significance of ebv dna load and eber.
Plasma epsteinbarr virus dna as an archetypal circulating tumour dna marker. There were 10 gaps in the k44mi ebv genome assembled, with gap lengths varying from 1 bp to 105 bp. Epsteinbarr virusencoded small rna in situ hybridization biopsy specimens were. When teens or young adults become infected, it can cause infectious mononucleosis, or mono. Compared with the reference ebv genome, a total of 1815 snps 146 indels. Complete genomic sequence of an epsteinbarr virusrelated herpesvirus. Ebv is a gammaherpesvirus of the lymphocryptovirus lcv genus and is closely related to other lcvs present in old world nonhuman primates, including ebv like viruses of chimpanzees and rhesus monkeys. You might know this disease better by its nickname, mono. Table 2 and figure 1 both show the breadth of genes that can be encoded.
Epsteinbarr is the virus that causes mononucleosis. Complete genome sequences have now been published for ebv baer et al. Epsteinbarr virus ebv is a doublestranded dna virus that belongs to the gammaherpesvirus subfamily and was discovered in a burkitts lymphoma bl cell. Eber2 is an abundant nuclear noncoding rna expressed by the epsteinbarr virus ebv. There are various types of dna sequences and chromosomal arrangements, including single.
To explore the overall organization of the functional ebv genome, we summarized viral gene expression, transcription. Kwok h, wu cw, palser al, kellam p, sham pc, kwong dlw, chiang aks. Epsteinbarr virus is a herpesvirus that causes infectious mononucleosis, carcinomas and immunoproliferative disease. Role of plasma ebv dna levels in predicting recurrence of. The microbiology society is a notforprofit organization. Its also called the kissing disease because of one way you can spread it to. Our current view of genome organization is based largely on, and perhaps is limited by, data derived mainly fromonlytwotypesofapproaches.
Request pdf ebv gene expression and regulation epsteinbarr virus ebv is an extremely efficient virus infecting the majority of the worlds adult population. The nuclear lamina in mammals, the genome is contained within the cell nucleus, a doublemembrane organelle that effectively segregates the transcription machinery from the cytoplasm, where protein production occurs. Prevalence of human papillomavirus hpv and epsteinbarr. In eastern countries, plasma levels of viral epsteinbarr deoxyribonucleic acid dna are accurate in predicting recurrence, but few data are available in western populations. At its lowest resolution, genome organization is guided by contacts with several nuclear substructures. Most people are infected by the epsteinbarr virus ebv in early childhood. Its genome encodes 86 proteins, which provided targets for a structural genomics project. Here, we report 40 fulllength ebv genome sequences obtained from matched oral wash. Review article medical progress columbia university. Genomewide analysis of wildtype epsteinbarr virus genomes. Furthermore, when hostvirus balance is not achieved, the virus can drive potentially. Genome diversity of epsteinbarr virus from multiple tumor types and normal infection. Ebv is an enveloped virus with icosahedral capsids symmetry and the genome takes on a linear form in mature virions and a circular episomal form during the period.
Epsteinbarr virus, frequently referred to as ebv, is a member of the herpesvirus family and one of the most common human viruses. Although oral cavity is located close to the nasal pharynx, the pathogenetic role of epsteinbarr virus ebv in oral cancers is unclear. Like other herpesviruses, ebv is a dna virus with a toroidshaped protein core that is. Ebv spreads most commonly through bodily fluids, primarily saliva. Parvoviruses are the only virus family with a singlestrand dna genome among the animal viruses. Ebv primarily infects b cells via the highaffinity receptor cd21. Most people get infected with ebv at some point in their lives. Ebv1 and ebv2 differ in the organization of the genes that code for the ebv nuclear antigen ebna2, ebna3a, ebna3b, and ebna3c. The symptoms of mono are extreme fatigue, fever, sore throat, and swollen lymph nodes. The virus itself is a dna strand that is composed of somewhere around 85 genes.
Thus the genes presently constituting the mammalian lineage likely stem from a combination of whole genomic amplifications and subsequent reductions of a much smaller genome. An overview of genome organization and how we got there. Complete genomic sequence of an epsteinbarr virusrelated. These proteins are important in regulating viral genes, replication of the viral dna, providing a structural component for the virions and monitoring the host immune response to the. To profile the ebv genome, we developed an efficient pipeline for aligning highthroughput sequencing reads to the viral genome and subtracting out human reads. Kmer counting was performing on tumor wgs reads aligned to the ebv genome using jellyfish version 2. Epigenetic specifications of host chromosome docking sites.
The nuclear envelope ne and its lamina are such structures. In some cases, primary infection can result in infectious mononucleosis. As the term implies, large genome dna viruses can also encode many more proteins. In fact, the rhesus monkey lcv and ebv share similar sequences and genetic organization, and are both capable of maintaining infection in the oropharynx and in b. Pdf occupancy of chromatin organizers in the epstein. When infection with ebv occurs during adolescence or young adulthood, it causes infectious mononucleosis 35% to 50% of the time. Detection of ebv infection and gene expression in oral. For the k4123mi ebv genome assembly, the ebvrelated sequences identified covered 99% of the lei et al. Small modifications of this pipeline can be used to map chip of viral transcription factors to the human genome.
Eukaryote genome organization of the have been dominated by a mixture of whole genome as well as piecemeal genome duplications. Early epsteinbarr virus genomic diversity and convergence. Role of viral and host micrornas in immune regulation of. Ebv gene expression and regulation human herpesviruses. To examine the presence of the ebv genome in specimens, eberish was performed using the inform eber probe ventana medical systems, inc. In contrast, doublestrand dna viruses can be subdivided into three groups. Lymphoproliferative disorders after hematopoietic stem. It usually causes no symptoms or only a brief, mild illness. Ebv noncoding rna binds nascent rna to drive host pax5 to. Epsteinbarr virus ebv is a ubiquitous human herpesvirus associated with the development of both lymphoid and epithelial tumours. Structure and organization of the hsv genome arrangement of sequence elements in hsv dna hsv1 virion dna is a linear molecule containing about 155 000 base pairs kieff et al. Epsteinbarr virus ebv is a gammaherpesvirus that infects a large fraction of the human population.
Our research spans both fields and so we recognize factors that are very obvious for those in one field, but less so for those in the other. Epstein barr is, like most viruses, extremely tiny. Epsteinbarr virus and cancer clinical cancer research. Epsteinbarr virus biological agents ncbi bookshelf. Pdf on feb 2, 2017, nick gilbert and others published genome organization. Novel ebv rnas and rna structures were identified by computational modeling and rnaseq analyses of ebv. Primary infection is often asymptomatic but results in lifelong infection, which is kept in check by the host immune system. Ebv is a herpesvirus with a 184kbp long, doublestranded dna genome that encodes 85 genes. To that end, sequencing the ebvpositive cancer cell genome provides a great solution to reveal the ebv integration distribution, the functional impact of viral integration on the host genome and the ebv genome characteristics. Locoregionally advanced nasopharyngeal carcinomas can be cured by the combination of chemotherapy and radiotherapy. The genome of epstein barr virus consists of a linear, doublestranded dna molecule that is 184 kilobase pairs in length. The positions of ebv genes and binding sites for ctcf and ebna1 are indicated. This study provides the first comprehensive genomewide survey of rna and rna structure in ebv. In general, the genome organization is less complex.
Little is known concerning the roles of rna structure in this important human pathogen. Genome diversity of epsteinbarr virus from multiple tumor. By mapping the natural ebv reads into the ebv reference genome nc007605. This molecular epidemiology study uses ebv genomic microarray ebvchip to simultaneously detect the prevalent rate and viral gene expression patterns in 57 oral squamous cell carcinoma biopsies. Dna revealed colinear genome organization with other gammaherpesviruses. Epsteinbarr virus, which is also known as human herpesvirus 4 hhv4 and which belongs to the herpesviridae family, has a doublestranded dna genome 10. Ebv genome strains, which she ould be useful r sources for ebvrelative studies.