Herpes simplex virus (HSV) can cause a wide range of diseases including skin lesions which are common, encephalitis which is rare, and HSV infection of the eye which is a leading cause of blindness in the U.S.A. Herpes virus infections are characterized by the ability of the virus to become latent. It is this ability, which leads to recurrent episodes of disease, and which is the focus of this grant. The overall goal is to understand the mechanism of HSV latency using both a mouse model system and human autopsy tissue. We have previously used the mouse model system of HSV latency to study the physical state of the latent viral genome. We now propose to examine the state of viral transcription in the latent state (Project 1). This will be done using the technique of in situ hybridization. We will also examine the steps involved in virus reactivation using topoizomerase inhibitors which we have recently shown inhibit reactivation in experimental ganglia though they do not inhibit normal virus growth (Project 2). To show that the mouse model accurately reflects the situation in human ganglia and brain, we will perform in situ hybridization, and other experiments where possible, to confirm the results from the mouse model (Project 3).
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