The Junctions between the Repetitive and the Short Unique Sequences of the Herpes Simplex Virus Genome Are Determined by the Polypeptide-coding Regions of Two Spliced Immediate-early mRNAs

Cunningham

McIntyre

et al. 1991

150

118

We report the determination of the DNA sequence of the long repeat (RL) region and adjacent parts of the long unique (UL) region in the genome of herpes simplex virus type 2 (HSV-2) strain HG52. The DNA sequences and genetic content of the extremities of HSV-2 UL were found to be closely similar to those determined previously for HSV-1. The 5658 bp sequenced at the left end of HSV-2 UL contained coding regions for genes UL1 to UL4 plus part of UL5. The 4355 bp sequenced at the right end Of UL contained coding regions for part of gene UL53, and the whole of genes UL54 to UL56. Comparison of the HSV-1 and HSV-2 UL56 sequences led to a correction in the published HSV-1 UL56 reading frame. The HSV-2 R L region, including one copy of the a sequence, was determined to be 9263 bp, with a base composition of 75-4% G+C and with many repetitive sequence elements. In HSV-2 RL, sequences were identified corresponding to HSV-1 genes encoding the immediate early IE110 (ICP0) transcriptional regulator and the ICP34.5 neurovirulence factor; the former HSV-2 gene was proposed to contain two introns, and the latter one intron. Downstream of the HSV-2 immediate early gene, the RE sequence encoding the latency-associated transcripts (LATs) was found to be dissimilar to that in HSV-1; the probable LAT promoter regions, however, showed similarities to HSV-1. Properties of the LAT sequences in both HSV-1 and HSV-2 were consistent with LATs being generated as an intron excised from a longer transcript.

Section: J Mcgeoch and Othersmentioning

confidence: 94%

Comparative Sequence Analysis of the Long Repeat Regions and Adjoining Parts of the Long Unique Regions in the Genomes of Herpes Simplex Viruses Types 1 and 2

Cunningham

McIntyre

et al. 1991

150

118

“…Our sequence analysis did not examine regions at the extremities of HSV-2 Us. These have been partly sequenced by Whitton & Clements (1984a). It is clear that at the left end of HSV-2 Us there exists a counterpart of HSV-1 gene US1, and that this accounts for all of this region of Us.…”

Section: Discussionmentioning

confidence: 99%

“…So far, these analyses have been limited in scope to individual genes and parts of genes, and to other, relatively small, functional sequences, including promoters and origins of replication (for instance, Swain & Galloway, 1983;McLauchlan & Clements, 1983;Whitton et al, 1983;Whitton & Clements, 1984a, b;Swain et al, 1985). In general, comparisons have shown corresponding regions to have closely related sequences, with occasional divergences and addition/deletion changes.…”

Section: Introductionmentioning

confidence: 99%

DNA Sequence and Genetic Content of the HindIII l Region in the Short Unique Component of the Herpes Simplex Virus Type 2 Genome: Identification of the Gene Encoding Glycoprotein G, and Evolutionary Comparisons

Moss

McNab

et al. 1987

165

120

SUMMARYThe DNA sequence was determined of the HindIII 1 fragment of herpes simplex virus type 2 (HSV-2), which is located in the short unique region of the HSV-2 genome. HindIII l was found to comprise 9629 base pairs. Comparison with the previously determined corresponding sequence for herpes simplex virus type 1 (HSV-1), and limited mRNA mapping, showed that HindIII l contained six genes (termed US2 to US7) and part of another (US8). The HSV-1 and HSV-2 sequences were found to be generally colinear~, with one major exception: the HSV-2 DNA contained an extra sequence of about 1460 base pairs, in the coding region of gene US4. By use of an antiserum raised against an oligopeptide representing amino acids near the C terminus of the predicted HSV-2 US4 polypeptide it demonstrated that this gene encodes the virion glycoprotein gG-2, while HSV-1 US4 encodes a much smaller virion glycoprotein with homology to the C-terminal portion of gG-2. Quantitative comparisons of the HSV-2 HindIII I and corresponding HSV-1 sequences showed that they had diverged by point mutation and by local addition and deletion, as well as by the major change in genes US4. It was found that within the HSV-2-specific part ofgG-2 there was a locality showing sequence similarity to a glycoprotein of pseudorabies virus (gX), and weaker similarity to glycoproteins D of HSV-1 and HSV-2. These data were interpreted to suggest, first, that HSV-2 US4 represents an ancient gene of alphaherpesviruses, and, more tentatively, that the evolution of the genes for gG and gD may have proceeded through a duplication event.

“…In HSV-1, the junctions are located 8 and 40 bp, respectively, from the initiating ATG codons in US12 and US1 (Murchie & McGeoch, 1982). Whitton & Clements (1984) proposed that the inverted repeats are capable of expansion during evolution to include sequences from Us, since the junctions in HSV-2 are located 1 and 33 bp from the corresponding ATG codons. They also concluded that expansion of the repeats may be limited by the locations of adjacent protein coding regions in Us.…”

Section: Gacgcc Ggttc Gaggcc T Cgggcgccccgc-c G Gccgtg T~ggcgcccgagc mentioning

confidence: 99%

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

Davison

1986

122

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