The objectives of this proposal are to define immune effectors of protection from HSV latency induced by vaccination with a replication-defective HSV mutant virus.
The specific aims are to quantify latency following challenge in immune and non-immune mice depleted and non-depleted or reconstituted with antibody, immune cell subtypes, and selected cytokines at the time of challenge. This focuses on an important puzzle in HSV pathology, namely how latency is established, maintained, and reactivated in the presence of a specific, vigorous, anamnestic immune response. Reactivation can have dire consequences. Stromal keratitis, a leading cause of blindness is considered an auto-immune disease and is associated with recurrent, not primary, HSV infection. The proposed research is designed to elucidate immune components involved in establishment and maintenance of latency and implicated in escape from latency and consequent initiation of disease, and to provide a model for testing vaccine and therapeutic strategies. The research design will be to vaccinate mice with replication-defective HSV and, following challenge with a virulent strain of HSV, to quantify latency in ganglia, the site of latent infection. Immune effectors of protection will be define using complement-mediated depletion, adoptive transfer, and immunohistochemistry. Latency will be quantified by in situ hybridization of the abundant latent viral RNA, LAT, and by in situ PCR.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI009841-03
Application #
2886287
Study Section
Virology Study Section (VR)
Program Officer
Beisel, Christopher E
Project Start
1999-09-30
Project End
Budget Start
1999-09-30
Budget End
2000-09-29
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115