INTRACEREBRAL RECOMBINANT HSV-1 VECTOR DOES NOT REACTIVATE LATENT HSV-1

Herpes simplex virus type-1 (HSV-1) has been used for gene delivery in the nervous system for the treatment of brain tumors and other neurol ogical diseases. In most protocols, recombinant viruses containing the gene of interest are directly injected into the brain. Since many peo ple harbor latent wild-type HSV-1 virus in sensory ganglia and other r egions of the nervous system, there is a potential risk that the injec ted recombinant virus may reactivate the latent wild-type virus to cau se severe encephalitis. The present study used two rat latent infectio n models to evaluate this risk. Adult rats were infected with wild-typ e kos by cornea scarification or by intracerebral injection, and after the establishment of latency, the ICP6(-) strain hrR3 was injected in tracerebrally. In the control group, the latent virus was reactivated by treatment of cadmium sulfate Viral shedding from tears was detected by incubation with Vero cells, and the trigeminal ganglia, cortical t issue and the eyes were collected to detect reactivated wild-type viru s by RT-PCR. Our results showed that while the reactivated wild-type v irus was readily detectable in the cadmium-sulfate-treated animals, in tracerebrally infected hrR3 did not reactivate the latent virus in eit her the cornea model or the cerebral model. These results indicate tha t intracranial infection of partially defective recombinant virus may bear little risk of reactivation latent wild-type virus harbored in th e sensory ganglia or the brain in our animal model.