1. Identification of ligand-receptor interactions across blood brain barrier in viral neuro-pathogenesis (EXTRA-MURAL Funding)
Team: Dr. Shashikant Vaidya (P.I.) & Ms. Durga Bethala (DST-INSPIRE-SRF)
Funding Agency: Department of Science and Technology, Govt. of India
Duration: March 2017 - Till date
Abstract:
More than 500 million people worldwide are infected each year by any of the four dengue virus (DENV) serotypes. Dengue serotype 2 (DENV 2) is most predominant in India and other South Asian countries. The clinical spectrum caused during dengue infections is wide, and some patients may develop neurological alterations during or after infection. Clinical evidence suggests that the blood-brain barrier (BBB) may be compromised during DENV infection; however, it is unclear whether the damage is due to the infection itself or to the inflammatory response activated by BBB cells.
Other neurotropic flaviviruses, such as Japanese encephalitis virus (JEV), are also known to cause neurological damage. JEV uses the bloodstream to enter nerve tissue, infecting cells of the neurovascular unit. Another neurotropic virus, rabies virus (RABV), uses the retrograde axonal route to infect neuronal cells. Both JEV and RABV affect neurovascular unit cells differently, resulting in BBB damage, glial activation, and tissue inflammation.
The aim of this project is to study the pattern of DENV infection in the BBB, compared with other neurotropic viruses like JEV and RABV using an in vitro model. Our study observed that the BBB is dysregulated by superinfecting DENV2-activated murine macrophages (RAW264.7) on murine endothelial cells (BEnd3), rather than by direct virus infection.