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1 Division of Virology, National Institute for Medical Research, Mill Hill, London NW7 1AA
2 Cancer Research Campaign Laboratories, Paterson Institute for Cancer Research, Wilmslow Road, Manchester M20 9BX
and3 Department of Virology, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 0NN, U.K.
More than 50 fragments resulting from complete digestion of the DNA of human herpesvirus 6 (HHV-6, strain U1102) with BamHI, EcoRI, HindIII, KpnI, NruI, SalI or SmaI have been isolated as clones in M13, plasmid, cosmid and lambda vectors. Using these clones, maps have been constructed for the fragments produced by nine restriction enzymes from unit-length virus genomes and from their concatemeric precursors. The unit-length genome is a linear, double-stranded molecule of 161.5 kbp composed of a central segment of a largely unique sequence of 141 kbp (U) with a sequence of 10 kbp duplicated in the same orientation at both left and right genomic termini (i.e. left and right copies of the direct repeat; DRL and DRR). Adopting as standard an orientation in which the major capsid protein gene is left of the gene for alkaline exonuclease, then the right genome termini and DRL. U junctions occur close to or within repetitive (GGGTTA)n sequences. Repetitions of short sequence motifs are present in at least two other regions of the genome. One of these regions consists of a simple repeat (T C/G) of approximately 1.5 kbp in length and is unstable as clones in bacterial vectors. The second region is stably maintained in such vectors and consists of a tandem array of at least 25 copies of a 110 bp sequence containing a single KpnI site. Comparisons of fragments arising from unit-length DNA with those from virus DNA from the nuclei of infected cells have shown that the concatemeric junctions in intracellular DNA contain head-to-tail dimers of the terminal duplications (i.e. ... U1.DRR1.DRL2.U2 ...). The gross structure established here for the genome from the U1102 isolate of HHV-6 resembles closely that suggested by Pellett and his colleagues for the Z29 isolate and differs from that of the five previously characterized human herpesviruses. This structure of HHV-6 DNA bears a superficial resemblance to that proposed for DNA from channel catfish virus and equine cytomegalovirus.
Present address: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, U.K.
> Present address: Department of Medicine, University of Cambridge, Cambridge CB2 2SP, U.K.
Present address: Department of Molecular Sciences, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K.
Received 8 August 1990;
accepted 17 September 1990.
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