Herpes virus infection is a very common recurrent health problem in humans, especially immuno suppressed individuals. After resolution of primary infection, a state of latency develops that persists until death. Environmental stimuli such as UV lead to periodic recrudescence of disease. The investigators have recently developed a powerful murine model of reactivated HSV disease of epithelium that is stimulated by a minimum UV exposure. This very closely mimics HSV epithelium disease in man, permitting study of cutaneous HSV-1 reactivation in a relevant experimental system. The studies proposed in this application will use this model to test the hypothesis that reactivated HSV-1 disease is due to a disruption in local cytokine balance, and disease resolution requires local cutaneous immunologic changes. They propose to study the immunopathology of HSV disease reactivation and suggest new treatments and vaccine strategies. They hypothesize that UV exposure results in secretion of soluble factors by keratinocytes that ultimately alter the TH1/TH2 balance which induces HSV from reactivation. Lack of CD4 responses in CD4 depleted animals then permit severe and prolonged disease. They propose that modulation of local immune factors including IL-12 and IFN-gamma alter the reactivation process and that differences of components of the local immune systems impact susceptibility to HSV-1 infection. Studies will be done in immune competent mice and in mice depleted of CD4 which yields reactivated HSV disease in a manner very similar to human HSV disease in HIV infected hosts. Specifically, they will characterize the immune response to HSV-1 at the local cutaneous level and to define the context of interplay of cytokines and immune cells during reactivated cutaneous HSV-1 disease; determine the role of infiltrating T lymphocytes in primary and reactivated disease in normal versus immune compromised models; and determine efficacy of genomic vaccine candidates in prevention of primary infection and in attenuation of reactivated disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE014138-01
Application #
6344428
Study Section
Special Emphasis Panel (ZDE1-YA (07))
Program Officer
Mangan, Dennis F
Project Start
2001-04-01
Project End
2006-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
1
Fiscal Year
2001
Total Cost
$292,500
Indirect Cost
Name
University of New Mexico
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
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Ye, Chunyan; Prescott, Joseph; Nofchissey, Robert et al. (2004) Neutralizing antibodies and Sin Nombre virus RNA after recovery from hantavirus cardiopulmonary syndrome. Emerg Infect Dis 10:478-82