The Herpes Simplex Virus Type 2 (HG52) Variant JH2604 Has a 1488 bp Deletion which Eliminates Neurovirulence in Mice

Taha, M Y; Clements, G. B.; Brown, Stuart A.

doi:10.1099/0022-1317-70-11-3073

Cited by 54 publications

(21 citation statements)

References 22 publications

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“…ICP34.5À mutants of HSV are usually avirulent following i.c. injection (3,6,(23)(24)(25)(26)(27)). Therefore, we tested whether the expression of GALV env RÀ alters this in normal rat brain by stereotaxic injection of OncoVEX GALV/CD into the forebrain.…”

Section: Galv Expression Causes Cell To Cell Fusion In Vitro a Panelmentioning

confidence: 99%

Combination of a Fusogenic Glycoprotein, Prodrug Activation, and Oncolytic Herpes Simplex Virus for Enhanced Local Tumor Control

Simpson¹,

Han²,

Liu³

et al. 2006

Cancer Research

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We have previously developed an oncolytic herpes simplex virus-1 based on a clinical virus isolate, which was deleted for ICP34.5 to provide tumor selected replication and ICP47 to increase antigen presentation as well as tumor selective virus replication. A phase I/II clinical trial using a version of this virus expressing granulocyte macrophage colony-stimulating factor has shown promising results. The work reported here aimed to develop a version of this virus in which local tumor control was further increased through the combined expression of a highly potent prodrug activating gene [yeast cytosine deaminase/uracil phospho-ribosyltransferase fusion (Fcy::-Fur)] and the fusogenic glycoprotein from gibbon ape leukemia virus (GALV), which it was hoped would aid the spread of the activated prodrug through the tumor. Viruses expressing the two genes individually or in combination were constructed and tested, showing (a) GALV and/or Fcy::Fur expression did not affect virus growth; (b) GALV expression causes cell fusion and increases the tumor cell killing at least 30-fold in vitro and tumor shrinkage 5-to 10-fold in vivo; (c) additional expression of Fcy::Fur combined with 5-fluorocytosine administration improves tumor shrinkage further. These results indicate, therefore, that the combined expression of the GALV protein and Fcy::Fur provides a highly potent oncolytic virus with improved capabilities for local tumor control. It is intended to enter the GALV/Fcy::Fur expressing virus into clinical development for the treatment of tumor types, such as pancreatic or lung cancer, where local control would be anticipated to be clinically advantageous. (Cancer Res 2006; 66(9): 4835-42)

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Section: Galv Expression Causes Cell To Cell Fusion In Vitro a Panelmentioning

confidence: 99%

Combination of a Fusogenic Glycoprotein, Prodrug Activation, and Oncolytic Herpes Simplex Virus for Enhanced Local Tumor Control

Simpson¹,

Han²,

Liu³

et al. 2006

Cancer Research

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show abstract

“…Virulence was with the insertion ofthe homologous HSV-1 fragment. Taha et al (14)(15)(16) described spontaneous HSV-2 deletion mutants, lacking less than 1.5 kbp at the termini of the L component, which were less virulent than a recombinant obtained by marker rescue.…”

mentioning

confidence: 99%

Replication, establishment of latency, and induced reactivation of herpes simplex virus gamma 1 34.5 deletion mutants in rodent models.

Whitley

Kern²,

Chatterjee³

et al. 1993

J. Clin. Invest.

175

146

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“…Mutants which fail to express ␥34.5 do not replicate in the brain or cause encephalitis following intracerebral inoculation of mice. [12][13][14][15] Lack of ␥34.5 expression does not impair virus replication in tissue culture in several cell types, 16 but replication is restricted in SK-N-SH neuroblastoma cells, 17 murine 10T1/2 cells, stationary phase primary mouse embryo cells 18 and 3T6 cells. 16 In addition, these mutants have been shown to be replication-defective and avirulent in SCID mice, 19 suggesting that their avirulence is an intrinsic property of the virus and is not a result of effective control by the immune system.…”

Section: Introductionmentioning

confidence: 98%

Potential and limitations of a γ34.5 mutant of herpes simplex 1 as a gene therapy vector in the CNS

et al. 1998

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The Herpes Simplex Virus Type 2 (HG52) Variant JH2604 Has a 1488 bp Deletion which Eliminates Neurovirulence in Mice

Cited by 54 publications

References 22 publications

Combination of a Fusogenic Glycoprotein, Prodrug Activation, and Oncolytic Herpes Simplex Virus for Enhanced Local Tumor Control

Combination of a Fusogenic Glycoprotein, Prodrug Activation, and Oncolytic Herpes Simplex Virus for Enhanced Local Tumor Control

Replication, establishment of latency, and induced reactivation of herpes simplex virus gamma 1 34.5 deletion mutants in rodent models.

Potential and limitations of a γ34.5 mutant of herpes simplex 1 as a gene therapy vector in the CNS

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