Herpes Simplex Virus (HSV) is the leading cause of infectious blindness in the US, largely due to its ability to persist within infected individuals in a latent state and periodically reactivate to cause recurrent lesions. Despite much study, the mechanisms of viral latency and reactivation are still not understood. Some information has been gained using HSV recombinants with mutations in specific genes, however such studies are limited by direct effects of mutations on viral replication which in turn affect the efficiency of establishment of latency. Thus, it has been impossible to distinguish whether these mutations affect replication alone or have additional affects on maintenance of latency or reactivation. In a novel approach, a transgenic mouse line will be generated which expresses the Cre recombinase specifically in neurons. Recombinant viruses will be created in which genes suspected to play a role in latency and reactivation will be flanked by loxP sites. The viruses will remain as wild-type during acute infection in peripheral epithelium, but as the viruses establish latency in neurons the presence of Cre will cause the deletion of viral sequences between the loxP sites resulting in inactivation of the targeted gene. These mice can then be examined for maintenance of latency and ability to reactivate relative to wild-type virus. Changes in the latency and reactivation profiles of Cre recombinase-deleted viruses will be demonstrative of specific roles for the deleted genes in the latency process.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32EY006997-01
Application #
6012696
Study Section
Special Emphasis Panel (ZRG1-EVR (03))
Project Start
1999-08-01
Project End
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Washington University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130