Viral therapy for central nervous system neoplasms: Studies using an ICP34.5 deficient herpes simplex virus in murine models

The development of Herpes Simplex Virus based vectors for therapeutic use in nervous system disorders is an important goal in the fields of virology and gene therapy. A detailed characterization understanding of the biology of attenuated viruses in CNS would be useful in determining the safety of this approach and in developing the most efficacious vector for a specific CNS disorder. The present studies characterize HSV-1 strain 1716, a mutant deficient in the ICP34.5 neurovirulence gene, as a vector in a murine brain tumor model using virological, immunohistochemical and molecular techniques. Specifically, I have shown that although the deletion in strain 1716 confers a neuroattenuated phenotype, the virus does replicate to a limited extent in murine CNS ependymal cells. Furthermore, strain 1716 does establish a latent infection in the CNS after intracerebral inoculation which is dependent upon the specific site of intracerebral inoculation. Finally, strain 1716, in a murine brain tumor model, can improve the survival of tumor bearing mice. Collectively, these results demonstrate that strain 1716 is an efficacious vector in a murine brain tumor model. With further study, a thorough understanding of this virus may lead to the development of HSV vectors for use in authentic human brain tumors