Herpes Simplex Virus Type I (HSV-1) infects humans orofacially, causing a gingivostomatis of the mouth and a keratitis of the eye. HSV-1 infections are highly prevalent in the population. Approximately eighty percent of adults in the U.S. are seropositive for HSV-1. Following a primary infection, this virus establishes a latent infection of the trigeminal from which it can reactivate causing a recurrence of the disease. Our present understanding of the pathogenesis of both latency and reactivation at the molecular level is incomplete. Research to date has established the importance of the LAT region in viral reactivation from the latent state. However no clear molecular role for the LAT region's contribution to reactivation has been defined, nor has the role of the LAT region in establishing a latent infection been determined. This proposal is aimed at the construction of more precisely defined mutations within the LAT region. Current viral mutants are defective in more than one function. A second goal of the proposal is to employ a variety of PCR and non-PCR-based techniques to study the ability of these mutant viruses to establish a latency infection when compared with the wild type virus. The final area of interest is to construct recombinant viruses which are unable to reactivate from the latent state and to learn from the structure of those viruses how the LAT region contributes to a reactivation event.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI045679-03
Application #
6532784
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Beisel, Christopher E
Project Start
2000-08-01
Project End
2005-05-31
Budget Start
2002-08-01
Budget End
2003-05-31
Support Year
3
Fiscal Year
2002
Total Cost
$272,721
Indirect Cost
Name
University of California Los Angeles
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Hamza, Mohamed A; Higgins, Dennis M; Feldman, Lawrence T et al. (2007) The latency-associated transcript of herpes simplex virus type 1 promotes survival and stimulates axonal regeneration in sympathetic and trigeminal neurons. J Neurovirol 13:56-66
Feldman, Lawrence T; Ellison, Aaron R; Voytek, Cynthia C et al. (2002) Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice. Proc Natl Acad Sci U S A 99:978-83