Grant: Operating Grant

The most common cause of a potentially fatal brain infection (encephalitis) is the result of a simple infection by a virus frequently found in humans. The herpes simplex virus is occasionally associated with such brain infections resulting in death in approximately 70% of those affected and untreated and a mortality still greater than 30% in those treated with specific antiviral therapy (acyclovir). How this virus causes brain infection is still poorly understood: It is thought that both virus multiplication and an inappropriate (exaggerated) immune response of the body causing inflammation may play a role in producing damages to the brain. The main hypothesis of our research proposal is that the immune response is critical to control herpes simplex virus multiplication in the brain early after viral infection but an overzealous and prolonged inflammatory response may also contribute to the high mortality rate encountered during this viral infection of the brain. Thus, we aim at better understanding the role of specialized brain and blood cells that respond to herpes simplex virus infection, especially those involved in the early immune response. In addition, we plan to evaluate the clinical benefits of various innovative therapies aimed at decreasing the inflammatory process in the brain in combination with standard antiviral therapy to improve the outcome of this viral infection. These modalities will be evaluated using animal (mouse) models that mimic the human disease. At term, our work should provide new insights into the mechanisms of this devastating brain disease and propose new strategies for treatment.