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).

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Microbiology and Infectious Diseases B Subcommittee (MID)
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Wistar Institute
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Tatarowicz, W A; Martin, C E; Pekosz, A S et al. (1997) Repression of the HSV-1 latency-associated transcript (LAT) promoter by the early growth response (EGR) proteins: involvement of a binding site immediately downstream of the TATA box. J Neurovirol 3:212-24
Fawl, R L; Gesser, R M; Valyi-Nagi, T et al. (1996) Reactivation of herpes simplex virus from latently infected mice after administration of cadmium is mouse-strain-dependent. J Gen Virol 77 ( Pt 11):2781-6
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Deshmane, S L; Valyi-Nagy, T; Block, T et al. (1995) An HSV-1 containing the rat beta-glucuronidase cDNA inserted within the LAT gene is less efficient than the parental strain at establishing a transcriptionally active state during latency in neurons. Gene Ther 2:209-17
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Mehta, A; Maggioncalda, J; Bagasra, O et al. (1995) In situ DNA PCR and RNA hybridization detection of herpes simplex virus sequences in trigeminal ganglia of latently infected mice. Virology 206:633-40
Gesser, R M; Valyi-Nagy, T; Fraser, N W et al. (1995) Oral inoculation of SCID mice with an attenuated herpes simplex virus-1 strain causes persistent enteric nervous system infection and gastric ulcers without direct mucosal infection. Lab Invest 73:880-9
Gesser, R M; Valyi-Nagy, T; Fraser, N W (1994) Restricted herpes simplex virus type 1 gene expression within sensory neurons in the absence of functional B and T lymphocytes. Virology 200:791-5
Tal-Singer, R; Eisenberg, R J; Valyi-Nagy, T et al. (1994) N-linked oligosaccharides on herpes simplex virus glycoprotein gD are not essential for establishment of viral latency or reactivation in the mouse eye model. Virology 202:1050-3
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