Herpes Simplex Virus Type I establishes latent infections in neurons of the peripheral and central nervous system from which it can periodically reactivate to cause lytic infection and recurrent orofacial disease. The state of the latent viral geno and the molecular mechanisms which control viral reactivation remain unknown. The objective of the proposed study is to characterize these features of latent infection. We will characterize the viral DNa present in latently infected tissues by constructing recombinant Herpes simplex viruses containing the Sup F (amber suppressor tRNA) gene. Latent viral DNA will be isolated using a novel bacteriophage DNA cloning protocol which will allow analysis of viral DNAs present at frequencies as low as one copy per 10-8 cells. We will characterize the molecular mechanisms which control viral reactivation by analysis of Chloramphenicol Acetyl-Transferase (CAT) RNAs and protein present in tissue infected with HSV-1 recombinant viruses which contain an HSV-1 alpha 4 promotor regulatory region coupled to the structural protein encoding sequence of the CAT gene. Determination of the state of the latent viral genome and the expression of alpha 4 gene products in infected tissues of the peripheral and central nervous systems should provide insight into the molecular basis for Herpes simplex virus reactivation. Elucidation of the molecular nature of Herpes simplex virus latency is research objective F03 of the Long Range Research Plan of the National Institute of Dental Research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS023949-01
Application #
3408074
Study Section
Virology Study Section (VR)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225