The immediate-early mRNA that encodes the regulatory polypeptide Vmw 175 of herpes simplex virus type 1 is unspliced.

SUMMARYA deletion mutant derived from herpes simplex virus type 1 (HSV-1) strain ANG was analysed. The deletion mapped within the polypeptide-coding region of the immediate-early ICP4 gene. Based on DNA sequence data the deletion was shown to comprise 84 base pairs. In the wild-type genome of strain ANG these sequences were almost completely homologous to the known sequences of HSV-1 strain 17. The ICP4 polypeptide induced by the mutant was similar in size to the wild-type ICP4 protein and was recognized by a monoclonal antibody against ICP4. The data presented suggest that the deletion corresponds to a region on the ICP4 polypeptide that is nonessential for the replication of the virus in vitro.

“…Cleavage of the cloned w.t. fragment with SmaI and HinfI yielded the same set of fragments that had been mapped previously by Rixon et al (1982) as shown in Fig. 2(a).…”

mentioning

confidence: 62%

mentioning

confidence: 99%

A Herpes Simplex Virus Type 1 Mutant with a Deletion in the Polypeptide-coding Sequences of the ICP4 Gene

Schröder

DeZazzo²,

Knopf

et al. 1985

“…2. Gene layout in the S segments of HSV-I and VZV• The HSV-1 mRNA locations were reported by Rixon et al (1982), Rixon & Clements (1982) and Rixon & McGeoch (1984, 1985. The locations of HSV-1 protein-coding regions (here called RS1 and US1 to US12) were described by Murchie & McGeoch (1982.…”

Section: Methodsmentioning

confidence: 99%

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

Davison

McGeoch

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

“…Mutational analysis of the IE175K protein has revealed that it is modular in 0001-2104 © 1994 SGM (Dobson et al, 1989). The IE175K promoter initiates RNA synthesis at several sites in the positions indicated (Mackem & Roizman, 1982;Murchm & McGeoch, 1982;Rixon et al, 1982). The likely TATA box motifs are indicated.…”

Section: Introductionmentioning

confidence: 99%

Binding and repression of the latency-associated promoter of herpes simplex virus by the immediate early 175K protein

Batchelor

Wilcox

O’Hare

1994

We demonstrate that the immediate early 175K protein (IE175K) of herpes simplex virus type 1 binds to the cap site of the latency-associated promoter (LAP) in an unusual manner. The complex formed on the LAP cap site was significantly larger than that formed on the IE175K cap site and the requirements for binding were qualitatively distinct with respect to both the prirnary sequence determinants at the site, and the regions of IE 175K protein required for binding compared to those for the IE175K cap site. Although purified IE175K was sufficient for this larger complex formed on the LAP cap site, the DNA-binding domain was unable to bind efficiently. This contrasted strikingly with the IE175K cap site where, using precisely analogous probes, the DNA-binding domain exhibited a strong interaction. Surprisingly, from dissociation kinetics we show that binding of the intact protein to the LAP cap site is considerably more stable than the binding of IE175K to its own cap site (half-lives of the complexes 15 min and < 1 min respectively), and this was reflected in more efficient repression of LAP-driven expression than IEI75K promoter-driven expression by IEI75K. Moreover, primary sequence requirements for IE175K binding to the LAP cap site region differed from previously identified IE175K recognition sequences in that in addition to a partially conserved consensus sequence, neighbouring bases were necessary for binding. Although the LAP cap site exhibits a pseudopalindromic arrangement of core consensus sites, we show that this is not the basis for the higher order, more stable binding to this region. Together these results indicate that IE175K forms an unusual complex at the LAP cap site, broadening the range of previously defined sequences recognized by IE175K.