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 the world are infected with the virus. EBV is 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 viral DNA replicates 100-fold or more, uses a third kind of viral origin of DNA replication, oriLyt, and many viral proteins. Here we 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 the DNA synthesis from these origins focusing, where practical, on recent advances in our understanding.

Regulation of Epstein–Barr virus reactivation from latency

“…Epstein–Barr virus can establish two types of infection in cells: latent and lytic (Fig. ) . In the latent state, its genomic DNA exists in the nucleus as an episome, is chromatinized with histones and expresses only a few latent genes (Fig.…”

The Epstein–Barr virus BRRF2 gene product is involved in viral progeny production

“…In the latent state, EBV genomic DNA exists in the nucleus as an episome, chromatinized with histones, and expresses only a limited number of viral latency genes (Lieberman, 2013). In the viral lytic cycle, all EBV lytic genes are expressed, potent viral DNA genome replication occurs, and progeny viral particles are produced (Hammerschmidt and Sugden, 2013;Tsurumi et al, 2005). Switching from latent to lytic states is called reactivation.…”

The Biology and Clinical Utility of EBV Monitoring in Blood

“…EBV DNA replicates by two distinct mechanisms (Hammerschmidt and Sugden 2013). In latently infected cells, EBV DNA is generally present as a closed circular nuclear plasmid.…”