Based on seroprevalence rates, between 150 and 200 million Americans are latently infected with herpes simplex virus (HSV). Most of the morbidity associated with HSV infections is a result of the repeated activation of latent virus that occurs throughout the lifetime of the host. Sensory neurons (dorsal root or trigeminal ganglia) serve as the reservoir for latent HSV-1. Currently, the mechanisms that trigger HSV reactivation are largely unknown, and it is not clear how recurrent herpetic disease occurs in the face of a seemingly vigorous immune response. Preliminary observations of elevated interleukin-10, interferon-gamma and RANTES mRNA in the trigeminal ganglia of latently infected mice suggest that T lymphocytes remain at the site of latent infection well beyond the resolution of acute disease. Furthermore, a hyperthermic stressor which induces HSV type-1 reactivation appears to be immunomudulatory, specifically, causing an increase in the transcription of these T cell-associated cytokine and chemokine mRNAs in latently infected trigeminal ganglia.
The specific aims of this application are to address the cell-mediated immune response to HSV-1 reactivation in neurons. Specifically, these studies will: 1) establish if T lymphocytes are recruited to the site of latent HSV-1 infection, 2) determine the effects of reactivation-inducing stressor on cytokine expression in neurons, 3) evaluate the role of T lymphocytes in controlling latent HSV-1 infection and facilitating virus clearance following stress-induced reactivation, and 4) determine the potential antiviral role of cytokines in HSV-1 reactivation. Collectively, these studies will provide fundamental knowledge regarding the role of T lymphocytes and their cytokines in the immune response to latent HSV-1 infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS035470-03
Application #
2703099
Study Section
Psychobiological, Biological, and Neurosciences Subcommittee (MHAI)
Program Officer
Kerza-Kwiatecki, a P
Project Start
1996-07-01
Project End
1999-10-31
Budget Start
1998-05-01
Budget End
1999-10-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
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