The clinical manifestations if herpes simplex virus (HSV) infections range in severity from trivial epithelial infections to fatal encephalitis, as well as presenting an increasing public health problem in the AIDS epidemic. After the initial infection, the virus can reactivate from the latent state, producing episodes of disease. Latency is central to the natural history of the disease, yet the mechanisms involved in the processes of the establishment, maintenance, and reactivation of latent HSV are not understood. Understanding HSV latency is important for the control and possible elimination of the diseases caused by HSV. Addition, information providing an understanding of the regulatory mechanisms involved in HSV latency may provide insight into other viral diseases, such as AIDS, where complex host-virus interactions regulate the outcome of the infection. We developed a model of herpes simplex virus latency in neurons in vitro and showed that nerve growth factor deprivation results in the reactivation of latent virus. To elucidate the mechanisms involved in the control of HSV latency, the model of HSV latency in neurons in culture will be used to: (1) Analyze viral transcription during each phase of the infection, determine the state of the viral genome during latent phase of the infection and determine the effects of HSV latency on the physiology of the neuron; (2) identify critical HSV genes involved in the establishment, maintenance and reactivation of latency; (3) define the role of protein phosphorylation to latency and reactivation; and (4) examine cell extracts from neuronal cultures harvested under conditions which support latency or reactivation for the presence or absence of DNA binding factors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29NS029046-01
Application #
3478193
Study Section
Experimental Virology Study Section (EVR)
Project Start
1991-01-01
Project End
1995-12-31
Budget Start
1991-01-01
Budget End
1991-12-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045