Evolutionary Comparisons of the S Segments in the Genomes of Herpes Simplex Virus Type 1 and Varicella-Zoster Virus

Abstract

SUMMARYThe genomes of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) consist of two covalently joined segments, L and S.,Each segment comprises an unique sequence flanked by inverted repeats. We have reported previously the DNA sequences of the S segments in these two genomes, and have identified protein-coding regions therein. In HSV-1, the unique sequence of S contains ten entire genes plus the major parts of two more, and each inverted repeat contains one entire gene; in VZV, the unique sequence of S contains two entire genes plus the major parts of two more, and each inverted repeat contains three entire genes. In this report, an examination of polypeptide sequence homology has shown that each VZV gene has an HSV-1 counterpart, but that six of the HSV-1 genes have no VZV homologues. Thus, although these regions of the two genomes differ in gene layout, they are related to a significant degree. The analysis indicates that the inverted repeats are evidently capable of largescale expansion or contraction during evolution. The differences in gene layout can be understood as resulting from a small number of recombinational events during the descent of HSV-1 and VZV from a common ancestor. INTRODUCTIONMembers of the family Herpesviridae are classified into three subfamilies: the Alpha-, Betaand Gamma-herpesvirinae. This subclassification is based on properties of the virus particle, on features of the replication cycle and on biological aspects, such as host range and site of latency (Matthews, 1982). These criteria have proved useful but, despite some attempts to include genome organization as an additional taxonomical factor, the evidence for relationships between the subfamilies has been circumstantial. Comparisons of currently emerging herpesvirus DNA sequences will allow the relationships to be investigated precisely and directly at the genetic level. For example, recent comparisons of sequences from herpes simplex virus type l (HSV-1) and Epstein-Barr virus, which are members of the Alpha-and Gammaherpesvirinae, respectively, have demonstrated a degree of conservation in the predicted amino acid sequences of at least three virus-coded proteins: the two subunits of the ribonucleotide reductase , the DNA polymerase (Quinn & McGeoch, 1985;Baer et al., 1984) and the major DNA-binding protein (Quinn & McGeoch, 1985). Nevertheless, the available evidence indicates that the Alphaherpesvirinae and Gammaherpesvirinae are rather distantly related. There are as yet no sequence data indicating the degree of relationship between the Betaherpesvirinae and the other subfamilies.In contrast, studies of antigenic relatedness and DNA homology have shown members of the same subfamily to be much more closely related. For example, Davison & Wilkie (1983), using the technique of DNA-DNA hybridization, detected conservation of several genes in five members of the Alphaherpesvirinae. They proposed from the colinear arrangement of conserved

Characterization of the Genome of Equine Herpesvirus 1 Subtype 2

“…11. Comparisons of gene organization in the S segments of HSV-1, HSV-2 and VZV indicate that the locations of the IRs/Us and Us/TR s junctions are defined by adjacent protein-coding regions (Davison & McGeoch, 1986). In HSV-1, the IRs/Us and Us/TRs junctions are located 8 and 40 bp, respectively, from the translation initiation codons of ORFs at each end of Us (Murchie & McGeoch, 1982).…”

“…Thus, Us appears to be the most divergent component of alphaherpesvirus genomes. Davison & McGeoch (1986) concluded from detailed comparisons of predicted amino acid sequences that each of the seven distinct genes in the VZV S segment has a counterpart in the HSV-1 S segment, but HSV-1 Us contains six genes which have no VZV homologues. Thus, these regions of the two genomes are related but, unlike the L segments, differ significantly in gene layout.…”

“…ORFs 3 and 4 are similar in location and orientation to their VZV counterparts, whereas ORFs 1 and 2 are similar to their HSV-1 counterparts, except that ORF 2 extends into TRs. Davison & McGeoch (1986) proposed an evolutionary model for the descent of the S segments of HSV-I and VZV from a common ancestor by a series of recombination events involving expansion or contraction of TRs/IRs to include or expel entire genes. The data presented here are consistent with the hypothesis that EHV-1 subtype 2 is also a product of this evolutionary pathway.…”

Identification of homologues to the human cytomegalovirus US22 gene family in human herpesvirus 6

“…Comparisons of these sequences have allowed the identification of genes common to all these viruses as well as the recognition of genes specific to either a particular virus or virus subgroup (Davison & McGeoch, 1986;Davison & Taylor, 1987;Kouzarides et al, 1987;Chee et al, 1990). Previous large scale sequence analysis of a 22 kbp region of HHV-6 strain U1102 (Lawrence et al, 1990) identified 17 ORFs, including those encoding highly conserved herpesvirus proteins such as the major capsid protein and alkaline exonuclease, and clearly demonstrated that HHV-6 and HCMV encode closely related proteins and have a similar organization of their coding sequences.…”

Varicella-zoster virus

“…The apparent collinear arrangement of hybridizing regions showed that detectably conserved genes are collinear in the two genomes and led to the hypothesis that other genes, for which the hybridization conditions were too stringent, might also be collinear. Subsequent comparison of the predicted amino acid sequences of VZV and HSV-1 proteins supported this (Davison & McGeoch, 1986;Davison & Scott, 1986;McGeoch et al, 1988). Of the 62 VZV proteins with HSV-1 counterparts, all but one are arranged collinearly.…”