Alphaherpesvirus DNA replication

DNA replication in alphaherpesviruses has been the subject of study in bursts over the years. Interest in the subject depends not just on simple curiosity about this central feature of the viral growth cycle, but also because DNA replication is a potentially useful target for antiviral therapy, as has already been shown with agents such as acyclovir. The viral contributions to the mechanism of genome replication are quite well understood but we still are unable to duplicate the in vivo situation in an in vitro assay. Much of the recent interesting work involves the host cell's contribution to the process, and this seems likely to remain a focus for the future. Structure of the genome There are over 30 alphaherpesviruses that infect a wide range of host species. Their genomes fall into two general categories, either herpes simplex (HSV) - like or varicella zoster (VZV) - like, with four or two, respectively, isomeric forms (Fig. 10.1). There is a wide range of G + C content (32%-75%), with a bias towards higher (>50%) numbers. There is also size heterogeneity (125-180 kbp) which, although quantitatively less than the nucleotide composition variation, may be much more significant for the lifestyle of the virus. All alphaherpesvirus genomes contain four general structural components: unique long and short (UL, US) sequences that encode single-copy genes and inverted repeat regions that bound the unique regions; these may contain diploid genes and sequences required for cleavage and packaging of viral DNA (Fig. 10.1).