Ocular Herpes Simplex Virus-1 (HSV-1) infection is a major cause of corneal scarring and blindness, mostly as a result of HSV-1 recurrences following establishment of latency. In rabbits and mice less than 10% of the HSV-1 genome is expressed during latency. Only one or two discrete HSV-1 genomic regions appear to be involved (Rock, Nesburn and Wechsler 1987). The RNA(s) and their potential proteins may play significant roles in initiation and/or maintenance of ocular (trigeminal ganglionic) HSV-1 latency. We have found similar transcriptionally active regions in latently infected human trigeminal ganglionic neurons (unpublished). In the rabbit ocular model of HSV-1 latency, reactivation and clinical recurrence can be readily induced. We will use this ocular model to study the HSV genes and gene products that are involved in establishment, maintenance, and reactivation of latent HSV-1 infection. We will map the genes expressed during latency and characterize the latency related RNAs (LR-RNAs) and their proteins. In vivo reactivation will be studied to determine what is occurring during the early hours of reactivation under """"""""normal"""""""" in vivo conditions, in an animal that suffers natural recurrences of HSV-1 ocular shedding. The ease of establishing latency and inducing reactivation in the ocular rabbit model will also allow us to analyze HSV-1 deletion mutants for latency and reactivation competency. Our long term goal is to use this information to develop efficacious modes of intervention in ocular HSV-1 infection, thereby alleviating a major cause of viral induced blindness. A detailed molecular understanding of ocular viral latency and reactivation should help lead to the development of methods for preventing the establishment and reactivation of HSV-1 latency in the ocular and nonocular setting. This also will be important in the development of an HSV-1 vaccine that does not itself establish latency.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007566-02
Application #
3264574
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1988-04-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
Perng, Guey-Chuen; Maguen, Barak; Jin, Ling et al. (2002) A novel herpes simplex virus type 1 transcript (AL-RNA) antisense to the 5' end of the latency-associated transcript produces a protein in infected rabbits. J Virol 76:8003-10
Perng, Guey-Chuen; Maguen, Barak; Jin, Ling et al. (2002) A gene capable of blocking apoptosis can substitute for the herpes simplex virus type 1 latency-associated transcript gene and restore wild-type reactivation levels. J Virol 76:1224-35
Perng, Guey-Chuen; Mott, Kevin R; Osorio, Nelson et al. (2002) Herpes simplex virus type 1 mutants containing the KOS strain ICP34.5 gene in place of the McKrae ICP34.5 gene have McKrae-like spontaneous reactivation but non-McKrae-like virulence. J Gen Virol 83:2933-42
Moxley, Michael J; Block, Timothy M; Liu, Hsi-Chou et al. (2002) Herpes simplex virus type 1 infection prevents detachment of nerve growth factor-differentiated PC12 cells in culture. J Gen Virol 83:1591-600
Samoto, Ken; Ehtesham, Moneeb; Perng, Guey-Chuen et al. (2002) A herpes simplex virus type 1 mutant with gamma 34.5 and LAT deletions effectively oncolyses human U87 glioblastomas in nude mice. Neurosurgery 50:599-605; discussion 605-6
Henderson, Gail; Peng, Weiping; Jin, Ling et al. (2002) Regulation of caspase 8- and caspase 9-induced apoptosis by the herpes simplex virus type 1 latency-associated transcript. J Neurovirol 8 Suppl 2:103-11
Inman, M; Perng, G C; Henderson, G et al. (2001) Region of herpes simplex virus type 1 latency-associated transcript sufficient for wild-type spontaneous reactivation promotes cell survival in tissue culture. J Virol 75:3636-46
Perng, G C; Slanina, S M; Ghiasi, H et al. (2001) The effect of latency-associated transcript on the herpes simplex virus type 1 latency-reactivation phenotype is mouse strain-dependent. J Gen Virol 82:1117-22
Perng, G C; Esmaili, D; Slanina, S M et al. (2001) Three herpes simplex virus type 1 latency-associated transcript mutants with distinct and asymmetric effects on virulence in mice compared with rabbits. J Virol 75:9018-28
Perng, G C; Jones, C; Ciacci-Zanella, J et al. (2000) Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science 287:1500-3

Showing the most recent 10 out of 39 publications