The role of blood-brain barrier integrity in herpes simplex virus neuropathology

The purpose of the proposed study is to understand to what extent reactivation and subsequent neurological dissemination of alphaherpesviruses are caused by functional impairments within the central nervous system (CNS).

The overall aim is to show how the integrity of the blood-brain barrier contribute to neuropathology by human herpes simplex viruses.

The hypothesis that age-induced disruption of the blood-brain barrier in elderly patients promotes both reactivation of latent herpes simplex virus and replication of the virus in the CNS causing encephalitis will be tested in a mouse model of induced blood-brain barrier disruption during the acute and the chronic phases of herpesvirus infection.

In parallel, we will characterize in detail the short- and long-term effects of blood-brain barrier damage on the CNS antiviral immune function.

These studies will reveal if a leaky blood-brain barrier promote alphaherpesvirus CNS infection and could also challenge current dogma on how these conditions arise in the elderly population.

Collectively, the results will reveal if the integrity of the CNS and the local immunity therein are crucial determinants of viral neuropathology.