EBV replication enzymes.

Abstract

The Epstein-Barr virus (EBV) can choose between two alternative life styles. It infects B lymphocytes, transforming them into lymphoblastoid lines and, in contrast to neurotropic herpesviruses such as herpes simplex virus type I that establish latency in nondividing neurons, must maintain its latent genomes in cells that have the potential to divide. In B lymphoblastoid cell lines established by EBV infection, the viral genome is maintained as covalently closed circular plasmids forming nucleosomal structures with histone proteins. The number of copies is maintained at 10–50 per cell to be duplicated once during each cell division cycle by the host cellular DNA replication machinery. When production of virus is induced, the circular genome becomes a ready template for amplification, generating thousands of copies per cell during lytic infection. Replication intermediates are head-to-tail concatamers, perhaps through a rolling-circle DNA replication, which are cleaved and packaged into infectious viral particles. The lytic phase of EBV DNA replication is dependent on seven viral replication proteins: BZLF1, BALF5, BMRF1, BALF2, BBLF4, BSLF1, and BBLF2/3 gene products. The BZLF1 protein is an oriLyt-binding protein and also acts as the lytic transactivator. The BALF5 gene encodes the DNA Pol catalytic subunit and the BMRF1 gene encodes the DNA Pol accessory subunit. They form a complex to act as the Pol holoenzyme. A single-stranded (ss)DNA-binding protein is encoded by the BALF2 gene.