title: Epigenetic Dysregulation in Virus-Associated Neoplasms.
abstract: The oncoproteins of human tumor viruses regularly interact with the cellular epigenetic machinery. Such interactions alter the epigenome of the host cell and reprogram its gene expression pattern. Altered levels or redistribution of (cytosine-5)-DNA methyltransferases and changes in the cellular methylome were observed in Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis B virus (HBV), hepatitis D virus (HDV), hepatitis C virus (HCV), and human papillomavirus (HPV) associated neoplasms and cell lines. Methylation-mediated silencing of cellular promoters was also noted in Merkel cell polyomavirus (MCPyV) positive Merkel cell carcinomas, and, as discussed elsewhere, in EBV-associated malignancies and adenovirus-induced rodent tumors as well. Promoter activation also occurred, either associated with DNA hypomethylation or with the induction of euchromatic histone modifications by viral oncoproteins. It is worthy to notice that HCV infection induced large, hypomethylated blocks of cellular chromatin, although the exact molecular mechanism remains to be elucidated. In hepatoma cells expressing HBx, the oncoprotein encoded by the HBV genome, demethylation of the repetitive satellite 2 sequences was observed, due to downregulation of the de novo DNA methyltransferase DNMT3B. Tax and HBZ, the oncoproteins of human T-cell lymphotropic virus type I (HTLV-I), can both activate and silence distinct cellular promoters by interacting with cellular enzymes involved in histone modification.
authors.affiliation: Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, Tisza Lajos krt. 64, H-6720, Szeged, Hungary.
authors.forename: Janos
authors.initials: J
authors.lastname: Minarovits
authors.affiliation: Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, Tisza Lajos krt. 64, H-6720, Szeged, Hungary.
authors.forename: Anett
authors.initials: A
authors.lastname: Demcsák
authors.affiliation: RT-Europe Nonprofit Research Center, Mosonmagyarovar, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Banati
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany. hans-helmut.niller@klinik.uni-regensburg.de.
authors.forename: Hans Helmut
authors.initials: HH
authors.lastname: Niller
mesh_terms: D002472:Cell Transformation, Viral; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014777:Virus Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014780:Viruses / Q000235:genetics / Q000378:metabolism*
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D014764:Viral Proteins
keywords: CpG island shores; CpG shelves; Epigenetic reprogramming; Focal hypermethylation; Histone acetyltransferases; Relocation of chromatin binding proteins; Viral oncoproteins