Herpes simplex virus (HSV) latency has been well characterized as an infection of the human nervous system, usually of sensory ganglion neurons. Latent HSV infections are the substrate of recurrent HSV infections and possibly other illnesses as well. Mechanisms for the establishment of HSV latency and reactivation of infection in neurons are largely unknown. In order to establish HSV latency, it is likely that the lytic HSV cascade need be diminished. It is hypothesized that this may be achieved partially by neuron-specific transcription regulators. Similar factors are likely to be involved in the reactivation process in latently infected neurons, since it is improbable that many neurons are destroyed by reactivation, although infectious virus is synthesized. HSV latency will be investigated in newborn mice, after neurectomy and in ganglion transplants, situations which are expected to alter neuronal transcription mechanisms. HSV RNA transcription will be studied by in situ and blot hybridization. Similarly, cellular transcriptional regulators of potential importance in control of the lytic infection will be studied by these techniques. Newly developed ganglion transplantation techniques will be utilized to investigate the molecular pathogenesis of HSV latency in terms of host factors and pharmacological agents that may interfere with the establishment of latency. Lastly, we will evaluate the likely non-neuronal site of at least some HSV latency and the effect of HSV infection on ganglion neuron function in studies of neuropeptide expression. HSV infection clearly alters in vivo neuronal function, although this has been uncommonly studied. These investigations will provide insights to the molecular and cellular basis of HSV latency, as well as an understanding altered neuronal functioning which results from HSV infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020684-10
Application #
2263941
Study Section
Experimental Virology Study Section (EVR)
Project Start
1984-07-01
Project End
1996-05-31
Budget Start
1994-06-01
Budget End
1995-05-31
Support Year
10
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Tenser, R B; Gaydos, A; Hay, K A (2001) Inhibition of herpes simplex virus reactivation by dipyridamole. Antimicrob Agents Chemother 45:3657-9
Tenser, R B; Gaydos, A; Hay, K A (1996) Reactivation of thymidine kinase-defective herpes simplex virus is enhanced by nucleoside. J Virol 70:1271-6
Hay, K A; Gaydos, A; Tenser, R B (1996) Inhibition of herpes simplex virus reactivation by dipyridamole in a mouse model. J Med Virol 50:198-203
Hay, K A; Gaydos, A; Tenser, R B (1995) The role of herpes simplex thymidine kinase expression in neurovirulence and latency in newborn vs. adult mice. J Neuroimmunol 61:41-52
Tenser, R B; Edris, W A; Gaydos, A et al. (1994) Secondary herpes simplex virus latent infection in transplanted ganglia. J Virol 68:7212-20
Tenser, R B; Hay, K A; Aberg, J A (1993) Immunoglobulin G immunosuppression of multiple sclerosis. Suppression of all three major lymphocyte subsets. Arch Neurol 50:417-20
Tenser, R B; Edris, W A; Hay, K A (1993) Neuronal control of herpes simplex virus latency. Virology 195:337-47
Tenser, R B (1991) Role of herpes simplex virus thymidine kinase expression in viral pathogenesis and latency. Intervirology 32:76-92
Tenser, R B; Viselli, A L; Savage, D H (1991) Reversible decrease of fluoride resistant acid phosphatase-positive neurons after herpes simplex virus infection. Neurosci Lett 130:85-8
Tenser, R B; Edris, W A; Hay, K A et al. (1991) Expression of herpes simplex virus type 2 latency-associated transcript in neurons and nonneurons. J Virol 65:2745-50

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