34 Epstein-Barr Virus

Abstract

Epstein-Barr virus (EBV) is fascinating and informative both as a human pathogen and as a replicon. EBV has become 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 although most people in the world are infected with the virus. EBV is maintained as an extrachromosomal replicon in infected normal and tumor cells. These viral plasmids replicate once per cell cycle, are licensed, require a single viral protein for their synthesis and segregation, but can use either of two functionally distinct origins of DNA synthesis for their replication. Viral progeny are not synthesized under these conditions, and the cells are said to be latently infected. This plasmid replication is consistent with survival of EBV’s host cells, and viral genes are required for proliferation and/or survival of the infected cells. EBV also has an additional mode of replication that is inconsistent with cell survival. Rare cells in an infected population change to support EBV’s lytic cycle in which viral DNA replicates 100-fold or more without cell division. Viral progeny are synthesized, and host cells die. This lytic mode of replication uses a third kind of viral origin of DNA synthesis and many viral proteins to carry out that synthesis. Here, we describe the three modes of EBV’s replication as a function of the viral origins used and the viral and cellular proteins that mediate initiation and elongation of DNA synthesis from these origins.