A herpes simplex virus type 1 mutant deleted for gamma 34.5 and LAT kills glioma cells in vitro and is inhibited for in vivo reactivation

Citation
K. Samoto et al., A herpes simplex virus type 1 mutant deleted for gamma 34.5 and LAT kills glioma cells in vitro and is inhibited for in vivo reactivation, CANC GENE T, 8(4), 2001, pp. 269-277
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER GENE THERAPY
ISSN journal
0929-1903 → ACNP
Volume
8
Issue
4
Year of publication
2001
Pages
269 - 277
Database
ISI
SICI code
0929-1903(200104)8:4<269:AHSVT1>2.0.ZU;2-#
Abstract
To create an oncolytic herpes simplex virus type 1 (HSV-1) that is inhibite d for reactivation, we constructed a novel herpes recombinant virus with de letions in the gamma 34.5 and LAT genes. The LAT gene was replaced by the g ene for green fluorescent protein, thereby allowing viral infection to be f ollowed. This virus, designated DM33, is effective in killing primary and e stablished human glioma cell lines in culture. DM33 is considerably less vi rulent following intracerebral inoculation of HSV-susceptible BALB/c mice t han the wild-type HSV-1 strain McKrae. The safety of this virus is further supported by the retention of its sensitivity to ganciclovir and its relati vely limited toxicity against cultured human neuronal cells, astrocytes, an d endothelial cells. The ability of DM33 to spontaneously reactivate was te sted in a rabbit ocular infection model that accurately depicts human herpe s infection and reactivation. Following ocular infection of rabbits, sponta neous reactivation was detected in 83% (15/18) of the eyes infected with wi ld - type McKrae. In contrast, none of the eyes infected with DM33 had dete ctable reactivation. The efficacy of this virus in cultured human glioma ce ll lines, its safety, confirmed by its inability to reactivate, and its att enuated neurovirulence make DM33 a promising oncolytic agent for tumor ther apy.