We have shown that herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) expression is important for HSV latency. Latency was defined by the usual criterion of the isolation of infectious virus during the period of latent infection. For the isolation of the virus it is necessary that (1) the latent infection be established and (2) that infectious virus can be reactivated. In the present proposal we plan to differentiate between the role of HSV TK expression for the establishment of latency and for the reactivation of the latent virus. To perform this detailed investigation of the mechanisms of latency we will perform studies with a temperature sensitive TK- mutant of HSV-1 and a mutant of HSV-1 containing a defined deletion in the TK gene. Studies will also be performed with TK mutants of HSV-2, including a deletion mutant to determine the importance of TK expression in the pathogenesis of infection. In vivo complementation to determine latency established by TK- HSV, rescue of the TK- HSV during latency, and detection of TK- HSV by in situ hybridization will be evaluated. In situ hybridization methodology will also be employed to investigate the presence of HSV specified RNA, including that for TK activity during latency. Finally, methods to inhibit and to chronize HSV reactivation will be utilized to permit study of the reactivation process. These detailed studies of the establishment of HSV latency and of reactivation will provide insights into the mechanisms of these processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020684-02
Application #
3401221
Study Section
Experimental Virology Study Section (EVR)
Project Start
1984-07-01
Project End
1991-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
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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