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Title: The DNA sequence of the RK strain of human herpesvirus 7
Author: Megaw, A. George
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1997
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Abstract:
Human herpesvirus 7 (HHV-7) was first isolated by Frenkel and colleagues in 1989 from CD4+ T- cells, during experiments concerning propagation of HHV-6. Uninfected cells underwent spontaneous cytopathic effect following conditions promoting T-cell activation. A new herpesvirus was isolated which was related to but distinct from human herpesvirus 6 (HHV-6) This virus was designated HHV-7 (RK). HHV-7 is ubiquitous in the human population - probably more than 85% of people are infected. It is likely that HHV-7 is transmitted through saliva, with primary infection occurring before three years of age. The virus has no proven involvement in any disease. HHV-7 is a member of the Betaherpesvirinae and is more closely related to HHV-6 than to human cytomegalovirus (HCMV). The genome is approximately 145 kbp in length and has an overall structure like that of HHV-6, consisting of a long unique region (U) flanked by a direct repeat (DR). Since 1984, the complete sequences of fourteen herpesvirus genomes have been published and at least four more have been completed. This has allowed comparative studies of individual genes and permitted extensive and detailed understanding of the relationships between the herpesviruses. In addition, recent reports based on molecular sequence analysis, have provided a detailed phylogeny and allowed an evolutionary timescale to be derived. The aims of this project were to determine the complete DNA sequence of HHV-7 and to analyse the coding potential of the sequence. The work was initiated in collaboration with Professor N. Frenkel (Tel-Aviv University, Israel), who provided genomic DNA from the RK strain. During the course of this work the complete DNA sequences of HHV-6 strain U1102 and HHV-7 strain J1 were published by other groups. Therefore, the HHV-7 strain RK sequence was compared with these two sequences in order to appraise evolutionary divergence and to reevaluate the genetic contents of HHV-6 and HHV-7. The HHV-7 RK genome was sequenced by direct shotgun cloning of random DNA fragments into an Ml3 vector. Approximately 7,000 fragments were sequenced and compiled into a database with the aid of a computer. The genetic content of the sequence was interpreted using a suite of computer programs. This analysis was then extended to reassess the sequence of HHV-6. Special attention was paid to potential splicing. The HHV-7 RK genome sequence obtained is 153,080 bp in length and comprises U (133,012 bp) flanked on each side by a copy of DR (10,034 bp). Four different reiterated sequences are present in the genome, two in U and two in DR. the latter comprise arrays of a human telomere-like element. Complexity and size resulted in one of these arrays being particularly challenging to resolve, and an unsatisfactory solution in this region is reflected in the likelihood that the sequence obtained is approximately 3 kbp longer than the actual genome. Analysis of the differences between HHV-7 RK and J! indicated that the lineages resulting in the two strains diverged from a common ancestor of the order of 10,000 years ago. It was concluded on the basis of various analytical criteria that the HHV-7 genome contains 84 genes, only one of which has no direct counterpart in HHV-6. However, the latter is related to an adjacent gene which has an HHV-6 homologue. By the same criteria, HHV-6 contains 85 genes, two of which lack counterparts in HHV-7. One encodes a putative membrane glycoprotein and the other is a homologue of the adeno-associated virus type 2 rep gene. Furthermore, sequence comparisons between HHV-7 and HHV-6 also allowed the identification of putative splice sites in eleven genes. One of these genes is predicted to encode a previously unrecognised membrane glycoprotein. This study lays the foundation for continuing experimental investigation of gene expression in HHV-7, particularly in regard to splicing.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.797103  DOI: Not available
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