Epstein-Barr virus (EBV) is a model of herpesvirus latency and epigenetic changes. The virus preferentially infects human B-lymphocytes (and also other cell types) but does not turn them straight into virus factories. Instead, it establishes a strictly latent infection in them and concomitantly induces the activation and proliferation of infected B cells. How the virus establishes latency in its target cells is only partially understood, but its latent state has been studied intensively by many. During latency, several copies of the viral genome are maintained as minichromosomes in the nucleus. In latently infected cells, most viral genes are epigenetically repressed by cellular chromatin constituents and DNA methylation, but certain EBV genes are spared and remain expressed to support the latent state of the virus in its host cell. Latency is not a dead end, but the virus can escape from this state and reactivate. Reactivation is a coordinated process that requires the removal of repressive chromatin components and a gain in accessibility for viral and cellular factors and machines to support the entire transcriptional program of EBV's ensuing lytic phase. We have a detailed picture of the initiating events of EBV's lytic phase, which are orchestrated by a single viral protein - BZLF1. Its induced expression can lead to the expression of all lytic viral proteins, but initially it fosters the non-licensed amplification of viral DNA that is incorporated into preformed capsids. In the virions, the viral DNA is free of histones and lacks methylated cytosine residues which are lost during lytic DNA amplification. This review provides an overview of EBV's dynamic epigenetic changes, which are an integral part of its ingenious lifestyle in human host cells.
Keywords: Chromatin; Herpesvirus; Infection; Latency; Reactivation.