Targeting the Blood-Brain Barrier to Limit Infection with Encephalitic Alphaviruses
Abstract
Venezuelan (VEEV) and Western (WEEV) equine encephalitis viruses are mosquito-transmitted alphaviruses that may infect the brain and cause fatal disease in humans. These viruses can also be spread via aerosolization, which means they could be used as bioterrorist agents. Viruses that enter the nasal cavity are able to enter the brain directly by climbing along connections from this area to the front part of the brain. Currently, there are no therapies or vaccines to mitigate or prevent fatal alphavirus brain infections. The brain is normally protected from viruses by the blood brain barrier (BBB), which refers to the inability of small molecules and cells to pass from the blood into the brain because of proteins (called “tight junctions”) that seal the spaces between cells that comprise the blood vessls. Studies have previously shown that alphaviruses that enter the brain after inhalation into may change how the BBB functions, allowing viruses and cells from the blood to enter more brain regions and cause disease. In preliminary studies, we have determined that brain blood vessels express proteins that “sense” viruses, which then causes them to either open or close the BBB by altering the function of tight junctions. In this application, our interdisciplinary team will utilize novel approaches for measuring tight junction opening and closing to the mechanisms that change BBB integrity in the context of alphavirus brain infections. We will define how viruses are sensed by the BBB, how they lead to changes in tight junction function, and identify new ways to block these effects in order to develop new drugs that prevent or treat alphavirus infections in the brain.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 26, 2016
- Source ID
- HDTRA11510032
Entities
People
- Robyn Klein
Organizations
- Defense Threat Reduction Agency
- Washington University in St. Louis