Neurotropism of herpes simplex virus type 1 in brain organ cultures

The mechanism of herpes simplex virus type 1 (HSV-1) penetration into the brain and its predilection to infect certain neuronal regions is unknown. In order to study HSV-1 neurotropism, an ex vivo system of mice organotypic brain slices was established and the tissue was infected with HSV-1 vectors. Neonate tissues showed restricted infection confined to leptomeningeal, periventricular and cortical brain regions. The hippocampus was the primary parenchymatous structure that was also infected. Infection was localized to early progenitor and ependymal cells. Increasing viral inoculum increased the intensity and enlarged the infected territory, but the distinctive pattern of infection was maintained and differed from that observed with adenovirus and Vaccinia virus. Neonate brain tissues were much more permissive for HSV-1 infection than adult mouse brain tissues. Taken together, these results indicate a complex interaction of HSV-1 with different brain-cell types and provide a useful vehicle to elucidate the mechanisms of viral neurotropism.