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| Original Article |
A herpes simplex virus type 1 mutant deleted for  34.5 and LAT kills glioma cells in vitro and is inhibited for in vivo reactivation |
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| Ken Samoto1,2, Guey-Chuen Perng3,4, Moneeb Ehtesham1,2, Yunhui Liu1,2, Steven L Wechsler3,4, Anthony B Nesburn3,4, Keith L Black1,2 and John S Yu1,2 |
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1The Maxine-Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048
2Department of Neurosurgery, University of California at Irvine, Irvine, California
3Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, Burns and Allen Research Institute, Los Angeles, California 90048
4Department of Ophthalmology, University of California at Los Angeles, Los Angeles, California
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Correspondence to: John S Yu, The Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8631 West Third Street, Suite 800 East, Los Angeles, CA 90048. E-mail: yuj@cshs.org
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| Abstract |
| To create an oncolytic herpes simplex virus type 1 (HSV-1) that is inhibited for reactivation, we constructed a novel herpes recombinant virus with deletions in the  34.5 and LAT genes. The LAT gene was replaced by the gene for green fluorescent protein, thereby allowing viral infection to be followed. This virus, designated DM33, is effective in killing primary and established human glioma cell lines in culture. DM33 is considerably less virulent following intracerebral inoculation of HSV-susceptible BALB/c mice than 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 relatively limited toxicity against cultured human neuronal cells, astrocytes, and endothelial cells. The ability of DM33 to spontaneously reactivate was tested in a rabbit ocular infection model that accurately depicts human herpes infection and reactivation. Following ocular infection of rabbits, spontaneous reactivation was detected in 83% (15/18) of the eyes infected with wild-type McKrae. In contrast, none of the eyes infected with DM33 had detectable reactivation. The efficacy of this virus in cultured human glioma cell lines, its safety, confirmed by its inability to reactivate, and its attenuated neurovirulence make DM33 a promising oncolytic agent for tumor therapy. Cancer Gene Therapy (2001) 8, 269-277 |
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| Keywords |
| Herpes simplex virus type 1 (HSV-1); gene therapy; glioma; green fluorescent protein; brain tumors |
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| April 2001, Volume 8, Number 4, Pages 269-277 |
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