Herpes simplex virus (HSV) is a common cause of human blindness due to recurrent infections targeting the cornea. The virus remains latent in the neurons of trigeminal ganglia after traveling by axonal transport from the original acute infection in corneal epithelium and stroma. A better understanding of how latency and reactivation are regulated for this virus is the key to developing strategies of protection and prevention. The general hypothesis is that latency and reactivation of HSV infection are regulated by cellular transcription factors that modulate genes needed for productive viral infection. HSV immediate early (IE) gene transcription may be repressed by cellular transcriptional factors or it may fail to be activated because of a lack of appropriate activating transcriptional factors to create latency. Viral IE gene transcription is reinitiated following a change in cellular transcription factors such as may occur following neuronal manipulation or systemic stress.
Specific aims of this project include: (1) to examine whether host proteins can regulate, and in doing so, activate HSV IE promoter transgenes in our transgenic mouse models without the presence of viral proteins; (2) to analyze our transgenic mouse models for up-regulation of each HSV IE promoter transgene using stimuli that represent natural means of reactivating this particular virus; and (3) to determine the significance in vivo, utilizing our transgenic mouse models, of the key regulatory sequence of HSV IE genes, TAATGARAT.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32EY007007-01A1
Application #
6134767
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Fisher, Richard S
Project Start
2000-04-01
Project End
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
1
Fiscal Year
2000
Total Cost
$42,628
Indirect Cost
Name
University of Missouri-Columbia
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211