This project is aimed at understanding aspects of the pathogenesis of herpes simplex virus (HSV) infection in the nervous system including the mechanism by which HSV infections are regulated within neurons during acute, latent, and reactivated infections. These studies which utilize a mouse model system and cultured cells should allow a better understanding of the pathogenesis of herpesvirus-induced disease in humans- During FY 1990 an HSV-2 RNA transcript which is expressed in neurons during latent infection has been characterized; this transcript is similar but not identical to the latency associated transcript of HSV-L. Further studies are in progress to define the differences between the latency associated transcripts of HSV-L and HSV-2. Despite numerous studies the role of these viral latency associated transcripts in regulation of HSV infections is not clear. Studies are in progress to define the characteristics of latent HSV-l infection in non-neuronal tissue. Experiments have been initiated to define a model for investigating the role of nerve growth factor and other host gene products in the regulation of viral gene expression during latent infection of neurons