Elimination of UL56 gene by insertion of LacZ cassette between nucleotide position 116030 to 121753 of the herpes simplex virus type 1 genome abrogates intraperitoneal pathogenicity in tree shrews and mice

Rösen-WoIff, Angela; Lamadé, Wolfram; Berkowitz, Cheryl; Becker, Yechiel; Darai, Gholamreza

doi:10.1016/0168-1702(91)90076-8

Cited by 32 publications

(19 citation statements)

References 32 publications

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“…The subsequent finding that this viral gene was transcribed in all pathogenic strains tested, but that the RNA was altered or missing entirely in all apathogenic HSV-1 strains which persist latently in the spleen [3,22] led to the correlation of UL56 gene activity with the pathogenicity and latency phenotype of HSV-1. This correlation was confirmed by the construction and characterization of a recombinant virus strain which lacks UL56 activity [25]. This strain, HSV-1-M-LacZ, contains the E. coli gene, under the control of the RSV promoter, in place of a deletion spanning from the carboxyterminus of UL55 (rip 116030) to the second exon ofIE110 (np 121753), which eliminates UL56 and the variable region of the BamH1 DNA fragment B, both of which were implicated in intraperitoneal pathogenicity and latency.…”

Section: Introductionsupporting

confidence: 55%

“…and persisted in the tissues for the duration of the experiment. For comparison, we studied DNA of the HSV-1 strain HFEM, which harbours a deletion of a DNA sequence containing the UL56 gene, known to be involved in intraperitoneal pathogenicity, which was implicated in the apathogenic phenotype in both tree shrews and mice [22][23][24][25]. In the present study HSV-1 (HFEM) DNA was detected only in the adrenal glands and then only transiently (on days 2 and 3 p.i.).…”

Section: Discussionmentioning

confidence: 92%

“…The HSV-1-M-LacZ strain was obtained from the laboratory of Professor G. Darai, University of Heidelberg, Heidelberg, FRG. This strain contains the E. coli [3-galactosidase (LacZ) gene which replaces a deletion of a nucleotide sequence that is implicated in intraperitoneal pathogenicity and latency [25].…”

Section: Virus Strainsmentioning

confidence: 99%

“…This strain, HSV-1-M-LacZ, contains the E. coli gene, under the control of the RSV promoter, in place of a deletion spanning from the carboxyterminus of UL55 (rip 116030) to the second exon ofIE110 (np 121753), which eliminates UL56 and the variable region of the BamH1 DNA fragment B, both of which were implicated in intraperitoneal pathogenicity and latency. While the host range and growth kinetics of this strain were comparable to the parental HSV-1 strain F, HSV-1-M-LacZ was unable to produce acute infection in animals [25].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 92%

Section: Virus Strainsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…It seems possible that UL56 plays a role in the Another hypothesis is that UL56 may play a role in the transport of viral glycoproteins to the site of secondary envelopment. While lack of the UL56 product does not affect viral replication in most types of cultured cells, it does markedly reduce the neuroinvasiveness of HSV-1 (3,36,37,38,39). Moreover, Kehm et al have shown that deletion of the Cterminal hydrophobic region of the UL56 protein abrogates the virulent phenotype (19).…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of the UL56 Gene Product of Herpes Simplex Virus Type 2

Koshizuka

Goshima

Takakuwa

et al. 2002

J Virol

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The UL56 gene product of herpes simplex virus (HSV) has been shown to play an important role in viral pathogenicity. However, the properties and functions of the UL56 protein are little understood. We raised rabbit polyclonal antisera specific for the UL56 protein of HSV type 2 (HSV-2) and examined its expression and properties. The gene product was identified as three polypeptides with apparent molecular masses ranging from 32 to 35 kDa in HSV-2-infected cells, and at least one species was phosphorylated. Studies of their origins showed that the UL56 protein of HSV-2 is also translated from the upstream in-frame methionine codon that is not present in the HSV-1 genome. Synthesis was first detected at 6 h postinfection and was not abolished by the viral DNA synthesis inhibitor phosphonoacetic acid. Indirect immunofluorescence studies revealed that the UL56 protein localized to both the Golgi apparatus and cytoplasmic vesicles in HSV-2-infected and single UL56-expressing cells. Deletion mutant analysis showed that the C-terminal hydrophobic region of the protein was required for association with the cytoplasmic membrane and that the N-terminal proline-rich region was important for its translocation to the Golgi apparatus and cytoplasmic vesicles. Moreover, the results of protease digestion assays and sucrose gradient fractionation strongly suggested that UL56 is a tail-anchored type II membrane protein associated with lipid rafts. We thus hypothesized that the UL56 protein, as a tail-anchored type II membrane protein, may be involved in vesicular trafficking in HSV-2-infected cells.

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Herpes simplex virus gene products: the accessories reflect her lifestyle well

Nishiyama

2004

Reviews in Medical Virology

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Herpes simplex virus (HSV) genomic DNA contains at least 74 distinct genes. A set of 40 genes, termed the 'core genes', is commonly found in all herpesviruses; their products include four capsid proteins, six DNA replication proteins, seven DNA packaging/cleavage proteins, four envelope glycoproteins, as well as several others. Although approximately half of the HSV genes are not essential for replication in cell cultures, all accessory gene products are predicted to play indispensable roles for viral replication and dissemination in vivo. Intensive studies have been undertaken to elucidate the functions and roles of HSV gene products, and we are now able to address, at least partially, the biological aspects of all HSV encoded proteins. This article is a brief summary of our present knowledge of the functions and roles of HSV gene products with special attention focused on UL14, UL34, UL51, UL56 and US3, all of which are thought to be involved in HSV egress. Furthermore, efforts are discussed to generate replication-competent HSV lacking a single or multiple accessory gene(s) for potential use in gene therapy or as anti-cancer therapeutics. Finally, specific HSV gene products are being explored as therapeutic agents.

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Elimination of UL56 gene by insertion of LacZ cassette between nucleotide position 116030 to 121753 of the herpes simplex virus type 1 genome abrogates intraperitoneal pathogenicity in tree shrews and mice

Cited by 32 publications

References 32 publications

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

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

Identification and Characterization of the UL56 Gene Product of Herpes Simplex Virus Type 2

Herpes simplex virus gene products: the accessories reflect her lifestyle well

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