Latent and Slow Virus Infection of the Nervous System, Multiple Sclerosis

Herpes simplex virus (HSV) latent infection of sensory ganglion neurons is the substrate of recurrent mucocutaneous HSV infection. In this context HSV latency is a prototypic latent viral infection of the nervous system, which undergoes periodic reactivation. During latency infectious virus and viral antigens are not detectable, and only a single species of viral RNA is present, the latency associated transcript (LAT). The goals in our laboratory have centered on understanding the pathogenesis of HSV latency in terms of biochemical factors important for the establishment-reactivation of latency, and also neuronal functions important in this process. Emphasis has been on the role of viral specified thymidine kinase expression, including the role of exogenous nucleosides, and secondly on latency after neuronal injury (e.g., neurectomy).

In pathogenesis studies we have utilized virological and immunological methods to demonstrate the criteria of HSV latency and in situ hybridization methods to demonstrate LAT. In other studies viral DNA after neurectomy was investigated by PCR methods. Investigations have largely been in vivo studies in mice, in which experimental surgery was used in conjunction with cell biology and molecular biology procedures. The emphasis in future studies will continue on the study of the pathogenesis of latent virus infection and reactivation, and disease of the nervous system. Toward this end, sensory ganglion transplantation is being utilized to investigate methods of this establishment of latency, and also mechanisms which control reactivation.