Grant: Operating Grant - Priority Announcement: Infection and Immunity (Bridge Funding)

Rabies is a serious problem in Canadian wildlife and it is an important public health problem in developing countries. An understanding of how rabies virus causes disease will be helpful in developing new strategies for the prevention and treatment of rabies and potentially also other viral and neurologic diseases. There is promising recent data from the laboratory of the principal applicant and others that rabies virus causes disease by injuring processes of neurons, including axons and dendrites. In particular, the infection likely causes damage by oxidative stress, which involves injury to tissues caused via by-products of the metabolism of oxygen called reactive oxygen species. Oxidative stress is important in a variety of human neurological diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis, and also in experimental infection of the brain in mice produced by herpes simplex virus. Using studies on cultured sensory nerve cells it will be determined the mechanisms by which rabies virus infection produces oxidative damage to neuronal processes. Tissues of mice experimentally infected with rabies virus and tissues from fatal cases of human rabies will also be studied for markers of oxidative stress. This work will give important insights into how rabies virus causes disease of the nervous system. This information will be important in the development of new therapies for patients with rabies and other viral diseases.