Immunological consequences of HSV-1-mediated gene transfer into the CNS

Defective HSV-1 viral vectors were prepared using amplicon methods. The amplicon contained the cytomegalovirus immediate-early promoter and the lacZ gene as a reporter in addition to the HSV elements required for replication and packaging in vitro. Viral vectors were stereotaxically injected into the rat dentate gyrus and the resulting expression and immune response were investigated. Beta-galactosidase activity was detected in several thousand neurons from as early as 24 hours to as late as 10 days after injection. A significant immune response to the vector inoculation developed, which was characterised by diffuse MHC class I up-regulation from 48 hours and the infiltration of MHC class II+ cells and activated T lymphocytes and macrophages from day 4. These features persisted for at least 31 days. Of particular interest was a small group of neurons in the posterior hypothalamus which were found bilaterally to express beta-galactosidase. The immune response at this distant uninjected site was delayed in onset but its features were similar to that found at the primary site of inoculation.