Therapy of experimental @entity1 @entity1313 using a XXXX mutant.

@entity1 @entity778 @entity70895 @entity1313 @entity19 @entity5 @entity189 @entity3307 @entity1968
BACKGROUND: @entity778 (HSV) strains previously have been shown to offer a potential therapeutic alternative to conventional treatment modalities for @entity1313 . Because HSV Type 1 strain 1716 has a deletion in the gamma 34.5 neurovirulence gene that renders it avirulent in the @entity19 central nervous system, we have assessed its potential to induce selective lysis of @entity5 cells versus neurons in vitro and in vivo. EXPERIMENTAL DESIGN: To do this, we studied parental @entity3307 17+ and strain 1716 using @entity1 @entity189 cells ( @entity70895 cells). These cells resemble neuronal progenitor cells and can be induced to differentiate into neurons (NT2N) with @entity1968 . Intracerebral grafts of @entity70895 cells into the brains of @entity19 resulted in lethal @entity1313 , and grafts of NT2N cells resulted in the integration of NT2N cells. RESULTS: In vitro studies showed that strain 1716 replicates in and spreads on monolayers of @entity70895 cells but not in NT2N cells. In vivo, strain 1716 replicated preferentially in @entity70895 @entity5 as evidenced by immunohistochemical staining for viral antigens, by in situ hybridization for HSV-specific transcripts, and by titration of virus from brains with @entity5 after intracranial injection of the virus into these @entity19 . The temporal regression of @entity70895 @entity5 in @entity19 treated with strain 1716 was demonstrated in vivo by magnetic resonance imaging. Electron microscopy and studies of DNA fragmentation suggested that regression of @entity70895 @entity1313 in strain 1716-treated @entity19 was mainly caused by a nonapoptotic, lytic mode of cell death. Finally, strain 1716-treated @entity70895 @entity5 -bearing @entity19 survived more than twice as long as mock-treated @entity5 -bearing @entity19 , and these differences in survival (25 vs. 9 weeks) were statistically significant (p < 0.03). CONCLUSIONS: We conclude from these studies that strain 1716 induces regression of @entity1 @entity5 established in the brains of @entity19 , resulting in their prolonged survival.
