Toxicity and neuronal infection of a HSV-1 ICP34.5 mutant in nude mice

Journal of Neurovirology
T M LasnerN W Fraser

Abstract

HSV-1 mutants in the RL-1 gene encoding the ICP34.5 protein have been demonstrated to have diminished neurovirulence in brain yet replicate as efficiently as parental virus in transformed tissue culture cells. Thus they have been proposed as candidates viruses for human brain tumor therapies. Evaluation of their replicative properties and pathogenesis within the nervous system has been limited. As most patients undergoing therapies for brain tumors are likely to be immunocompromised, it will be important to understand the pathogenesis of these viruses in immunocompromised hosts. To this end, the lateral ventricle of nude mice was injected with high (2.5 x 10(7) PFU), medium (10(5) PFU), or low dose (10(3) PFU) HSV-1 variant-1716, which has a deletion in the RL-1 gene. Ten of 10 mice died within 2-3 days following the high titer infection. Six of 19 animals with medium titer infection died within 9 days, and viral antigens were seen in ependymal cells as well as neurons within the brainstem and thalamus. Although only two of 19 animals became moribund 18 days after medium titer viral infection, many neocortical and hippocampal neurons were positive for HSV-1 antigens. However, plaque-purified viral isolates recovered from brain ...Continue Reading

Citations

Apr 5, 2000·The Journal of Clinical Investigation·R L Martuza
Aug 10, 2000·Neoplasia : an International Journal for Oncology Research·A JacobsC Fraefel
Dec 22, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·T TodoR L Martuza
Apr 11, 2006·Cancer Gene Therapy·Y Shen, J Nemunaitis
Mar 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Peter C HuszthyRolf Bjerkvig

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