Determination of the nucleotide sequence flanking the deletion (0.762 to 0.789 map units) in the genome of an intraperitoneally avirulent HSV-1 strain HFEM

Koch, Hans-Georg; Rösen, Angela; Ernst, Fedor; Becker, Yechiel; Darai, Gholamreza

doi:10.1016/0168-1702(87)90073-6

Cited by 17 publications

(5 citation statements)

References 14 publications

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“…We therefore speculate that transcription of these genes may initiate within UL, downstream of these sites. In strain HFEM of HSV-1 there is a deletion whose endpoints correspond to residues 117 087 and 120 640 in our sequence, and this been shown to confer an apathogenic phenotype on virus inoculated into mice intraperitoneally (Koch et al, 1987;Ben-Hur et al, 1988). The only functional elements which we can see the deletion removing are the presumed control sequences for gene UL56.…”

Section: Discussionmentioning

confidence: 96%

The DNA Sequences of the Long Repeat Region and Adjoining Parts of the Long Unique Region in the Genome of Herpes Simplex Virus Type 1

Perry

McGeoch²

1988

Journal of General Virology

166

110

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SUMMARYWe have determined the DNA sequence of the long repeat region (RL) in the genome of herpes simplex virus type 1 (HSV-1) strain 17, as 9215 bp of composition 71.6~ G + C. In addition, the sequences of parts of the long unique region (UL) adjacent to the terminal (TRL) and internal (IRL) copies of RL were determined (2611 and 3836 bp, respectively). Gene organization in these regions of UL was deduced from the sequences and other available data. It was proposed that the region of UL sequenced, adjacent to TRL, contains three complete genes, none with significant previous characterization, and that the region of UL adjacent to IRL also contains three genes, one encoding the immediate early protein IE63. The RL sequence contains one well characterized gene, for the protein IEll0, whose organization we have described previously. Between the downstream end of the IE110 gene and UL there is a 3500 bp segment of RL in which we did not find convincing protein-coding sequences, and which thus remains of obscure functionality. Upstream of the IEll0 gene is a region previously proposed by others to contain a gene. However, our sequence data are not compatible with their interpretation. We do consider it possible that the region is protein-coding, but regard gene organization here as still unresolved. INTRODUCTIONThe genome of herpes simplex virus type 1 (HSV-1) consists of a linear, double-stranded DNA of some 152000 bp (see McGeoch et al., 1988a). The DNA is regarded as consisting of two covalently linked segments, termed the long (L) and short (S) regions. Each of these contains a unique sequence (UL and Us) which is flanked by a pair of oppositely oriented repeat sequences (RL and Rs). The terminal and internal copies of RL are termed TRL and IRL ; similarly for Rs. This structure is shown in Fig. 1. The genome also possesses a terminal redundancy of 400 bp, termed the a sequence, and at the internal 'joint' between the L and S segments there are one or more further copies of the a sequence, oppositely oriented to the terminal copies. In a productively infected cell, an inversion process operates at the internal a sequence so that the progeny virion DNA population consists of a mixture of four sequence-orientation isomers which differ in the relative orientations of their L and S segments. One isomer is designated as the prototype for mapping purposes (Roizman, 1979).We have been engaged in general sequence determination of the genome of HSV-1 strain 17, and have published sequences for Us (McGeoch et al., 1985), Rs (McGeoch et al., 1986) and UL (McGeoch et al., 1988a). In this paper we report the complete sequence for RL, of 9200 bp, together with adjacent parts of UL. This work has allowed precise definition of the boundaries between UL and the flanking copies of RL, and of the organization of genes in UL adjacent to those junctions. RL contains one well characterized gene, encoding the immediate early (IE) transcriptional activator IE110, whose sequence we have previously described (Perry et al.,

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Section: Discussionmentioning

confidence: 96%

The DNA Sequences of the Long Repeat Region and Adjoining Parts of the Long Unique Region in the Genome of Herpes Simplex Virus Type 1

Perry

McGeoch²

1988

Journal of General Virology

166

110

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“…The DNAs differ with respect to their size and base composition. [204], and HHV1 strain HFEM [123,126]). The size of the viral genomes is characteristic of each virus (species) and is not a reflection of polymorphism even though individual herpesvirus genomes vary slightly in size.…”

Section: Herpesvirus Genomesmentioning

confidence: 99%

The familyHerpesviridae: an update

Roizmann

Desrosiers

Fleckenstein

et al. 1992

Archives of Virology

488

208

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“…Peles et al [17] showed that the apathogenic HSV-1 strain HFEM was unable to replicate in the adrenal glands or penetrate the spinal cord and brain after intraperitoneal injection. The recombinant virus HSV-1-M-LacZ, in which a 4.1 kbp sequence which is deleted in HFEM [10,19] was reinserted into the viral genome, regained the ability to replicate in the adrenal glands. This recombinant virus, however, was unable to penetrate the spinal cord.…”

Section: Introductionmentioning

confidence: 97%

Herpes simplex virus type 1 (HSV-1) UL56 gene is involved in viral intraperitoneal pathogenicity to immunocompetent mice

Berkowitz

Moyal

Rösen‐Wolff³

et al. 1994

Archives of Virology

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A comparison of the pathogenicity in mice of the recombinant herpes simplex virus type 1 (HSV-1) strain HSV-1-M-LacZ, in which the UL56 gene has been deleted, was made with its parental strain F, following infection in different mouse strains. The polymerase chain reaction (PCR) technique was used to study the migration of virus DNA in the mouse model. Tissues from adult mice infected intraperitoneally (IP) with one of three HSV-1 strains (F, HFEM or HSV-1-LacZ) were examined for the presence of viral DNA. DNA of the pathogenic strain F was detected in the adrenal glands, spinal cord, brain, liver and pancreas. DNA of HSV-1-M-LacZ was detected in the same tissues. However, DNA of the apathogenic strain HFEM was detected transiently (on days 2 and 3 p.i., but not days 1, 5 or 7), only in the adrenal glands and no viral DNA was detected in any of the other tissues. HSV-1 pathogenic strains injected intraperitoneally into newborn mice (7 days old) killed most of the mice. In the surviving mice viral DNA of the three virus strains was found in peritoneal exudate cells (PEC), adrenal glands, spinal cord, liver and spleen. It was found that HSV-1-M-LacZ, which lacks the UL56 gene, resembled in pathogenicity to the newborn mice the pathogenic HSV-1 strains F and KOS. The PCR technique was used to trace viral DNA in tissues of the mice which survived HSV-1 infection at 7 weeks of age. Only HSV-1 (KOS) DNA was detected in the pancreas. The brains of these mice did not contain viral DNA. It is suggested that HSV-1 DNA may reside in surviving HSV-1- infected newborn mice in a "latent" state in nonneural tissues.

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Determination of the nucleotide sequence flanking the deletion (0.762 to 0.789 map units) in the genome of an intraperitoneally avirulent HSV-1 strain HFEM

Cited by 17 publications

References 14 publications

The DNA Sequences of the Long Repeat Region and Adjoining Parts of the Long Unique Region in the Genome of Herpes Simplex Virus Type 1

The DNA Sequences of the Long Repeat Region and Adjoining Parts of the Long Unique Region in the Genome of Herpes Simplex Virus Type 1

The familyHerpesviridae: an update

Herpes simplex virus type 1 (HSV-1) UL56 gene is involved in viral intraperitoneal pathogenicity to immunocompetent mice

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