Genetic comparison of human alphaherpesvirus genomes

Abstract

Human herpesviruses 1, 2 , and 3 (herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and varicella-zoster virus (VZV)) have been classified as alphaherpesviruses based originally upon their biological properties, and subsequently on the sequences of their respective genomes (Minson et al ., 2000; Pellett and Roizman, in press). All of these viruses maintain latent infections in sensory ganglia, and can productively infect a variety of human cells, including the living cells of mucous membranes and skin. These epithelial sites also provide exit points for the virus to infect other individuals. The structure of the genomes of the alphaherpesviruses that infect humans are quite similar at first glance (Fig. 5.1). All have two unique segments that are flanked by repeats of different lengths. The unique segments are designated short (S) and long (L) and the repeats designated as internal (IR) or terminal (TR). Members of the genus simplexvirus (HSV-1 and HSV-2) exist as four roughly equimolar isomers, each isomer differing in the relative orientations of the long and short components. The orientation of one of the HSV isomers has been designated prototypical, and could therefore be designated TRL-U L -IRL-IRS-U S -TRS. VZV also produces 4 genomic isomers, but those in which the long component is inverted are significantly reduced in frequency, to about 5% of total genomes. It is tempting to speculate that this is a consequence of the shorter repeats flanking the VZV long component (88.5 bp) as compared to the repeats flanking U S in human alphaherpesviruses (6000–7400 bp) and U L in HSV-1 and HSV-2 (around 9,000 bp).