We have determined the DNA sequence of the long unique region (UL) in the genome of herpes simplex virus type 1 (HSV-1) strain 17. The UL sequence contained 107943 residues and had a base composition of 66-9~ G+C. Together with our previous work, this completes the sequence of HSV-1 DNA, giving a total genome length of 152260 residues of base composition 68.3~ G+C. Genes in the UL region were located by the use of published mapping analyses, transcript structures and sequence data, and by examination of DNA sequence characteristics. Fifty-six genes were identified, accounting for most of the sequence. Some 28 of these are at present of unknown function. The gene layout for UL was found to be very similar to that for the corresponding part of the genome of varicella-zoster virus, the only other completely sequenced alphaherpesvirus, and the amino acid sequences of equivalent proteins showed a range of similarities. In the whole genome of HSV-1 we now recognize 72 genes which encode 70 distinct proteins. INTRODUCTION In the last decade, the study of animal viruses has been revolutionized by the application of nucleic acid sequencing techniques to viral genomes. Many smaller virus genomes have been completely sequenced, and the sequences interpreted to give high resolution views of the genetic organization and the nature of the encoded proteins, while comparisons of sequences have enhanced our understanding of relationships between viruses. For larger virus genomes, total determination of nucleotide sequence remains a formidable undertaking, and only two complete sequences of virus genomes larger than 105 residues have been published. These are for the gammaherpesvirus Epstein-Barr virus (EBV) of 172282 residues (Baer et al., 1984) and the alphaherpesvirus varicella-zoster virus (VZV) of 124884 residues (Davison & Scott, 1986a). In this paper we report a third complete herpesvirus genome sequence, that of herpes simplex virus type 1 (HSV-1), which comprises 152260 residues. The molecular biology and genetics of HSV types 1 and 2 have been widely investigated such that overall they are the most extensively characterized of the family Herpesviridae. A decade ago, studies on the structure of HSV DNA showed it to be a linear molecule which could be viewed as consisting of two covalently linked segments, designated long (L) and short (S). Each segment contains a unique sequence flanked by a pair of inverted repeat sequences, as shown in Fig. 1. The long repeat (RL) and short repeat (Rs) sequences are distinct. The molecule also
Previous work has shown that transcriptional activation of herpes simplex virus type 1 (HSV-1) immediate early genes is mediated by a protein species (Vmw65) present in the tegument of infecting virions. This paper describes DNA sequence analysis and mRNA mapping of the Vmw65 gene in HSV-1 strain 17. The Vmw65 coding region was identified as a 490 codon sequence encoding a polypeptide of molecular weight 54,342 and characterised by a high proportion of charged amino acid residues. A homologue to Vmw65 was detected in the genome of varicella-zoster virus, another human herpesvirus. Apart from its role in trans-activation, Vmw65 is a major constituent of the virion. Its possible significance in virus structure is discussed.
SUMMARYThe herpes simplex virus type 1 (HSV-1) polypeptide Vmw65 is a structural component of the virus particle and is also responsible for trans-induction of immediate early (IE) transcription. Functional domains of this polypeptide were investigated by constructing a series of 10 plasmids each with a 12 bp insertion in the gene encoding Vmw65. Plasmids were analysed for their ability to stimulate IE transcription in short term transfection assays, and the altered Vmw65 polypeptides were assayed for the ability to form an IE-specific protein-DNA complex (IEC) in vitro. A direct correlation was observed between stimulation of transcription and formation of IEC, strongly suggesting that IEC is an important intermediate in transcription activation. Plasmids were also tested for their ability to rescue the temperature-sensitive mutation in the HSV-2 assembly mutant ts2203, since marker rescue analysis indicated that this mutation maps within the gene encoding Vmw65. Five plasmids failed to rescue ts2203, thereby defining regions of Vmw65 required for virus assembly. The results show that distinct domains exist in Vmw65 for activation of transcription and assembly of virus.
Two of the loci represent the well-known genes for DNA polymerase and major DNA-binding protein, but the remainder had little or no previous characterization. In this report we present the DNA sequences of the five newly identified genes and their deduced transcript organizations and encoded amino acid sequences. These genes were designated UL5, UL8, UL9, UL42, and UL52 and were predicted to encode proteins with molecular weights of, respectively, 99,000, 80,000, 94,000, 51,000, and 114,000. All of these genes had clear counterparts in the genome of the related alphaherpesvirus varicella-zoster virus, but only UL5 and UL52 were detectably conserved in the distantly related gammaherpesvirus Epstein-Barr virus, as judged by amino acid sequence similarity. The sequence of the UL5 protein, and of its counterparts in the other viruses, contained a region closely resembling known ATP-binding sites; this could be indicative, for instance, of a helicase or primase activity.
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