Brack-Werner Lab

The BBB is a highly impermeable barrier that prevents the free passage of molecules resulting in limited access to the brain parenchyma. These physical attributes pose a challenge in identifying antivirals capable of targeting neurotropic viruses. To develop predictive BBB screening models, we utilize in vitro cultures of human brain microvascular endothelial cells (HBMEC), human brain microvascular pericytes (HBMVP), and a human neural stem cell line (HNSC.100). The validation of these models involves a combination of assays measuring barrier tightness, cell marker expression, and an established cell line for HIV drug discovery (EASY-HIT).

The current knowledge of cellular targets and host responses induced by neurotropic viruses is largely based on in vitro single cell culture systems and post-mortem brain samples, which are limited. To further investigate known and novel cellular targets, we employ our in vitro BBB models with viruses that include TBEV and other human pathogenic flaviviruses, including West Nile and Zika virus. With these infection models we can further investigate the host responses induced by these viruses that may provide insight to their neuropathology.

Despite the availability of a TBEV vaccine, the inactivated vaccine requires revaccination every 3 years and the vaccination rates in Europe are low. This results in a larger population susceptible to TBEV infection and its severe manifestations, including encephalitis that may result in coma and death. Therefore, it is imperative to discover TBEV-specific antivirals to fight infections in the exposed unvaccinated or immunosuppressed individuals.