Grant: Operating Grant

Herpes simplex virus (HSV) is the most common cause of sporadic, potentially fatal brain infection in North America. The mortality rate associated with HSV encephalitis is approximately 70% in the absence of treatment and still greater than 30% despite specific antiviral therapy with acyclovir. How HSV causes encephalitis is still poorly understood: it is thought that both virus replication and the indirect immune response causing inflammation may play a role in producing damage to the central nervous system. The main hypothesis of our research proposal is that cerebral immunity is critical to control HSV replication in the brain early after viral infection but that an overzealous and prolonged inflammatory response may also contribute to the high mortality encountered during HSV encephalitis. Thus, we aim at better understanding the role of cerebral immunity during this viral infection, especially the innate (early) immune response provided by specialized cerebral cells called microglia. In addition, we will assess the beneficial effects of various immunomodulatory therapies in combination with potent antiviral agents on the outcome of HSV encephalitis in a validated mouse model. At term, our work should provide new insights into the mechanisms of this devastating viral disease and innovative strategies for treatment (anti-inflammatory compounds) and prevention (vaccines).