Invasion of a murine in vitro blood?brain barrier co?culture modelby dengue virus serotypes 1 to 4

AbstractThe blood-brain barrier (BBB) is a physical barrier that restricts the passage of cells and molecules as well as pathogensinto the central nervous system (CNS). Some viruses enter the CNS by disrupting the BBB, while others can reach the CNSwithout altering the integrity of the BBB. Even though dengue virus (DENV) is not a distinctive neurotropic virus, the virusis considered to be one of the leading causes of neurological manifestations. In this study, we found that DENV is able tocompromise the integrity of a murine in vitro blood-brain barrier (BBB) model, resulting in hyperpermeability, as shown bya significant increase in sucrose and albumin permeability. Infection of brain endothelial cells (ECs) was facilitated by thepresence of glycans, in particular, mannose and N-acetyl glucosamine residues, on cell surfaces and viral envelope proteins,and the requirement for glycan moieties for cell infection was serotype-specific. Direct viral disruption of brain ECs wasobserved, leading to a significant decrease in tight-junction protein expression and peripheral localization, which contributedto the changes in BBB permeability. In conclusion, the hyperpermeability and breaching mechanism of BBB by DENV areprimarily due to direct consequences of viral infection of ECs, as shown in this in vitro study