Herpesvirus DNA Replication

The genomes of herpesviruses are linear double-stranded DNA molecules ranging in size from 120 kb to more than 200 kb. Although the many different herpesviruses display a wide variety of tissue tropisms and vary enormously in the way in which they interact with their natural hosts, one common feature of the biology of all herpesviruses is the mechanism by which they replicate their genomes during the lytic phase of the replication cycle. Lytic DNA replication in every herpesvirus studied occurs by a mechanism that generates long head-to-tail concatemers of viral genomes that are cleaved to unit-length genomes during the process of encapsidation. This common mode of lyticDNA replication reflects a conserved set of viral genes encoding the basic components of the replication machinery. Another common feature of herpesvirus biology is the capacity to remain latent in the infected host, but, unlike the case with lytic DNA replication, the mechanism by which the viral genomes are maintained during latency apparently differs considerably among the herpesviruses. The cells that harbor latent genomes are different for the different viruses, and perhaps the more intimate relationship between viral and host chromosomal replication during latency accounts for the greater diversity of mechanism. For example, EpsteinBarr virus (EBV), which is latent in dividing B cells, is replicated during latency from a latency-specific origin called oriP that is distinct from the origin of lytic DNA replication. Replication in this system requires a single virus-encoded protein (EBNAl) and is apparently carried out by the chromosomal replication machinery (see Yates, this volume). On the other hand, herpes simplex virus (HSV) is latent in postmitotic neurons, and there is no evidence for any viral DNA replication during latency. In this review, I focus on lytic DNA replication, with an emphasis on studies of HSV DNA replication, the herpesvirus system about which most is known.