Epigenetic dysregulation of the host cell genome in Epstein-Barr virus-associated neoplasia.
Epstein-Barr virus (EBV), a human herpesvirus, is associated with a wide variety of malignant tumors. The expression of the latent viral RNAs is under strict, host-cell dependent transcriptional control. This results in an almost complete transcriptional silencing of the EBV genome in memory B-cells. In tumor cells, germinal center B-cells and lymphoblastoid cells, distinct viral latency promoters are active. Epigenetic mechanisms contribute to this strict control. In EBV-infected cells, epigenetic mechanisms also alter the expression of cellular genes, including tumor suppressor genes. In Nasopharyngeal Carcinoma, the hypermethylation of certain cellular promoters is attributed to the upregulation of DNA methyltransferases by the viral oncoprotein LMP1 (latent membrane protein 1) via JNK/AP1-signaling. The role of other viral latency products in the epigenetic dysregulation of the cellular genome remains to be established. Analysis of epigenetic alterations in EBV-associated neoplasms may result in a better understanding of their pathogenesis and may facilitate the development of new therapies.
Institute for Medical Microbiology and Hygiene at the University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany. Hans-Helmut.Niller@klinik.uni-regensburg.de
Hans Helmut
HH
Niller
Hans
H
Wolf
Janos
J
Minarovits
D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology; D019175:DNA Methylation / Q000235:genetics* / Q000502:physiology; D044127:Epigenesis, Genetic; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000821:virology; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D011401:Promoter Regions, Genetic; D014764:Viral Proteins / Q000378:metabolism; D017735:Virus Latency / Q000235:genetics / Q000502:physiology
D014764:Viral Proteins