26 Epstein-Barr Virus DNA Replication

Abstract

Epstein-Barr virus (EBV) and its close relatives are the only known viruses that have two fully independent systems for replicating their genomes, one that supports virus production during active or “lytic” infection, and a second one that operates during latent stages of infection to allow the circular viral genomes to be duplicated during each cell division cycle. Although EBV’s system of lytic DNA replication is for the most part a heritage of the herpesvirus family, its system for replication during latency is entirely its own. During latent infection, while the genes required for lytic replication and virus production are silent, the circular EBV chromosome is replicated by the cell’s DNA replication machinery, apparently only once during each S phase. This arrangement of having the host cell replicate its genome during latency is probably related to the fact that EBV establishes latency in cells that are prone to divide. EBV appears to maintain its life-long infection of people by residing within B cells (Klein 1994; Miyashita et al. 1995), and, during the initial phase of latent infection of B cells, EBV expresses a small set of genes that together cause the cells to proliferate (Kieff and Leibowitz 1990; Miller 1990). EBV DNA replication during latency might also be important for the eventual productive infection of epithelial cells, because EBV appears to be most able to infect undifferentiated epithelial cells but to replicate lytically in differentiated cells (Sixbey 1989).

EBV replication during latency relies almost entirely on the cell. A single EBV-encoded...