To understand better the long-term neurobiological interactions and effects of herpesvirus infection on host sensory ganglia, a mouse model has been developed in which evidence indicating neurite sprouting has been documented. At present we are determining whether these sprouts successfully regrow and reestablish connections in the CNS. If regeneration in this model can be demonstrated, then these studies, in addition to defining herpes-induced host neurobiological alterations, will provide new insight into the requirements for regeneration when compared with classical axon injury paradigms. Initial studies examine the effects of herpes simplex virus type-2 (HSV-2) infection on host dorsal root ganglia (DRG) following a peripheral footpad inoculation. This experimental model mimics many aspects of human clinical herpesvirus infection and may, in addition, provide insights into mechanisms of post- herpetic neuralgia. During FY 1994, the following issues were addressed: (1) Can neurochemical alterations, that have been demonstrated in classical axotomy-induced regeneration models, be identified here? In a time-course study of HSV-2 infection, alterations of growth-associated protein (GAP-43), a marker usually identified with regeneration in neurons, was analyzed in DRG cell bodies and in their peripheral and central processes. (2) Can neurites be demonstrated in this model and do they contain GAP-43? Neurites have been observed incidentally in dorsal roots in another HSV model, but current studies aim to systematically examine this question at the ultrastructural level in this model. The primary findings were that in this model: (1) GAP-43 is increased in DRG, dorsal roots, and glial cells 2 weeks after inoculation. This result is further evidence that, following acute ganglionic HSV-2 infection, selective neurochemical alterations can be found in DRG neurons, and another indication that the molecules that are selectively induced may relate to neuronal regrowth. (2) Preliminary ultrastructural evidence indicates that neurites are present in the dorsal roots of HSV-infected mice in this model.
