Replication of Epstein-Barr viral DNA

Abstract

Epstein-Barr virus (EBV) is a paradigm for human tumor viruses: it is the first virus recognized to cause cancer in people; it causes both lymphomas and carcinomas; yet these tumors arise infrequently given that most people in theworld are infected with the virus. EBVis maintained extrachromosomally in infected normal and tumor cells. Eighty-four percent of these viral plasmids replicate each S phase, are licensed, require a single viral protein for their synthesis, and can use two functionally distinct origins of DNA replication, oriP, and Raji ori. Eightyeight percent of newly synthesized plasmids are segregated faithfully to the daughter cells. Infectious viral particles are not synthesized under these conditions of latent infection. This plasmid replication is consistent with survival of EBV's host cells. Rare cells in an infected population either spontaneously or following exogenous induction support EBV's lytic cycle, which is lethal for the cell. In this case, the viralDNA replicates 100-fold or more, uses a third kind of viral origin ofDNAreplication, oriLyt, and manyviral proteins. Herewe shall describe the three modes of EBV's replication as a function of the viral origins used and the viral and cellular proteins that mediate theDNAsynthesis fromthese origins focusing,where practical, on recent advances in our understanding. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.