Flaviviruses such as Japanese encephalitis virus (JEV), West Nile virus (WNV), Yellow Fever virus (YFV) and Zika virus, can infect neuronals cells and cause neuronal damages, when given access to the central nervous system (CNS).
The blood-brain barrier (BBB) is the main interface between the blood and the CNS. It is composed of endothelial cells and maintained by cross-talk of endothelial cells with astrocytes and pericytes. It regulates the brain homeostasis and controls the cellular and molecular traffic between blood and brain. Many viruses can cross this barrier by different mechanisms : direct infection the endothelial cells, crossing by infected immune cells, disruption of the BBB following peripheral infection, passing between cells without disruption of the BBB and transcytosis.
To date, little is known about neurotropic Flavivirus neuroinvasiveness. Our study aims at determining the cellular markers and viral determinants of Flavivirus neuroinvasiveness, using an in vitro model of human BBB composed of human endothelial cells hCMEC/D3 and human neuroblastoma cells SK-N-SH. We compared BBB crossing of wt JEV RP9 virus strain with that of JEV vaccine strain SA14-14, and found that our in vitro BBB model could discriminate between the 2 viruses. Both viruses are unable to infect the hCMEC/D3 cells after they form a barrier. Moreover, transcriptomic analyses of the hCMEC/D3 cells after either wt or vaccine strain crossing did not show any significant difference, suggesting that the particle transport across the BBB might be done through similar mechanisms (C. Khou et al, in preparation).