The Epstein-Barr virus (EBV) can choose between two alternative lifestyles; latent or lytic replication. In the latent state, the EBV genomic DNA, which exists as a closed circular plasmid, appears to behave just like host chromosomal DNA and it has recently been demonstrated that replication of OriP-containing plasmid is indeed dependent on the cellular initiation factors, ORC2 and Cdt l. Here, current concepts of how chromosomal DNA replication origins are determined by the initiation proteins in mammalian cells are first summarized and then possible mechanisms of OriP interaction with cellular initiation proteins are covered. Furthermore, differences between OriP-containing plasmids and the EBV genome are discussed with reference to replication.

In the viral productive cycle, the EBV genome is amplified 100- to 1000-fold. Intermediates of viral DNA replication are found as large head-to-tail concatemeric molecules, probably resulting from rolling-circle DNA replication. The lytic phase of EBV DNA replication is dependent on seven viral replication proteins. In this section, their biochemical characterization is summarized and we propose models for the initiation step and the replication fork. Finally, we contrast EBV replication proteins with other prokaryotic and eukaryotic DNA replication proteins.