Latent and lytic Epstein-Barr virus replication strategies

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 been demonstrated recently that replication of OriP-containing plasmids is indeed dependent on the chromosomal initiation factors, ORC2 and Cdt1. On the other hand, in the viral productive cycle, the EBV genome is amplified 100- to 1000-fold by the viral replication machinery. EBV productive DNA replication occurs at discrete sites in nuclei, called replication compartments and the lytic programme arrests cell cycle progression and changes the cellular environment greatly. It has been revealed recently that the EBV lytic programme promotes an S-phase like cellular condition, which most favours viral lytic replication. This review describes recent advances regarding the molecular basis of EBV DNA replication during latent and lytic infections and then refers to cellular circumstances after induction of the lytic replication of EBV. Based on the molecular mechanism for the EBV lifestyle, purposeful induction of the lytic form of EBV infection is now advocated as one of the strategies for specific destruction of Epstein-Barr virus (EBV)-associated malignancies where the virus is latently infected.