title: Epigenetic Alterations in Epstein-Barr Virus-Associated Diseases.
abstract: Latent Epstein-Bar virus genomes undergo epigenetic modifications which are dependent on the respective tissue type and cellular phenotype. These define distinct viral epigenotypes corresponding with latent viral gene expression profiles. Viral Latent Membrane Proteins 1 and 2A can induce cellular DNA methyltransferases, thereby influencing the methylation status of the viral and cellular genomes. Therefore, not only the viral genomes carry epigenetic modifications, but also the cellular genomes adopt major epigenetic alterations upon EBV infection. The distinct cellular epigenotypes of EBV-infected cells differ from the epigenotypes of their normal counterparts. In Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC) significant changes in the host cell methylome with a strong tendency towards CpG island hypermethylation are observed. Hypermethylated genes unique for EBVaGC suggest the existence of an EBV-specific "epigenetic signature". Contrary to the primary malignancies carrying latent EBV genomes, lymphoblastoid cells (LCs) established by EBV infection of peripheral B cells in vitro are characterized by a massive genome-wide demethylation and a significant decrease and redistribution of heterochromatic histone marks. Establishing complete epigenomes of the diverse EBV-associated malignancies shall clarify their similarities and differences and further clarify the contribution of EBV to the pathogenesis, especially for the epithelial malignancies, NPC and EBVaGC.
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
authors.forename: Hans Helmut
authors.initials: HH
authors.lastname: Niller
authors.affiliation: RT-Europe Nonprofit Research Center, Mosonmagyarovar, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Banati
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 17177, Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Salamon
authors.affiliation: Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, Tisza Lajos krt. 64, H-6720, Szeged, Hungary. minimicrobi@hotmail.com.
authors.forename: Janos
authors.initials: J
authors.lastname: Minarovits
mesh_terms: D000818:Animals; D002472:Cell Transformation, Viral; D044127:Epigenesis, Genetic; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014764:Viral Proteins
keywords: Epigenetic signature; Genome-wide demethylation; Heterochromatic histone marks; Host cell methylome; Viral epigenotypes