Role of epigenetics in EBV regulation and pathogenesis.

Epigenetic modifications of the viral and host cell genomes regularly occur in EBV-associated lymphomas and carcinomas. The cell type-dependent usage of latent EBV promoters is determined by the cellular epigenetic machinery. Viral oncoproteins interact with the very same epigenetic regulators and alter the cellular epigenotype and gene-expression pattern: there are common gene sets hypermethylated in both EBV-positive and EBV-negative neoplasms of different histological types. A group of hypermethylated promoters may represent, however, a unique EBV-associated epigenetic signature in EBV-positive gastric carcinomas. By contrast, EBV-immortalized B-lymphoblastoid cell lines are characterized by genome-wide demethylation and loss and rearrangement of heterochromatic histone marks. Early steps of EBV infection may also contribute to reprogramming of the cellular epigenome.