Both serotypes of herpes simplex virus (HSV), HSV-1 and HSV-2, are aetiological agents of genital herpes, although genital herpes caused by HSV-1 recurs less frequently. The HSV-1 genome contains a number of short, tandemly repeated sequences, and some reiterated sequences can serve as sensitive markers for the differentiation of HSV-1 strains. In the present study, variation in reiterations (assumed to be due to different copy numbers of tandemly repeated sequences) was examined in HSV-1 isolates from genital lesions from the same individual. Six sets (three primaryrecurrence sets and three multiple-recurrence sets) of HSV-1 isolates were analysed: the primaryrecurrence set consisted of two isolates (one isolated at a primary episode and the other at a recurrent episode) from the same individual; the multiple-recurrence set consisted of plural isolates from different episodes of recurrence in the same individual. Variations in length of the major DNA fragment, containing reiteration I (within the a sequence) and/or reiteration IV (within introns of genes US1 and US12), were detected between isolates of each multiple-recurrence set, but not of the primary-recurrence set. Thus, HSV-1 isolates of multiple-recurrence sets are assumed to have diverged more widely within each set than those of primary-recurrence sets, probably because of more rounds of virus DNA replication. This divergence of reiterations seems to indicate a forward step in the division of HSV-1 from a common ancestor into different lineages.
INTRODUCTIONHerpes simplex virus (HSV) is a ubiquitous human pathogen which latently infects neural cells of spinal ganglia and is classified into two serotypes, HSV-1 and HSV-2 (Dolan et al., 1998;Everett, 2000;McGeoch et al., 1988;Preston, 2000). HSV-1 is common in general populations and is often acquired non-sexually during childhood years. Although there is evidence that the majority of genital herpes infections are HSV-2-related, an increase in HSV-1 genital infection in at least some countries (e.g. UK, USA and Japan) has been suggested (Hashido et al., 1997(Hashido et al., , 1998 Kawana et al., 1982;Lafferty et al., 2000;Ribes et al., 2001;Stanberry et al., 1999;Vanderhooft & Kirby, 1992;White & Wardropper, 1997). HSV-1 genital infection is less likely to recur than that caused by HSV-2 (Kinghorn, 1993;Lafferty et al., 1987;Mertz et al., 1990;Sucato et al., 1998;Taylor et al., 1999).The genome of HSV-1 is a 152 kb linear duplex DNA molecule (McGeoch et al., 1988) (Fig. 1a). Epidemiologically unrelated HSV-1 strains can usually be differentiated by analysing variations in restriction endonuclease (RE) cleavage patterns (Buchman et al., 1978(Buchman et al., , 1980 Chaney et al., 1983; Lonsdale et al., 1980). Variations in RE cleavage patterns between HSV-1 strains are divided into two types (Umene et al., 1984;Umene & Yoshida, 1989, 1993 Umene, 1998a, b). One type of variation, termed 'restriction fragment length polymorphism' (RFLP), is due mostly to a gain or loss of an RE cleavage site and causes a ...