RT Journal Article SR Electronic T1 Comparative analysis of neuroinvasion by Japanese encephalitis virulent and vaccine strains in an in cellulo model of human blood-brain barrier JF bioRxiv FD Cold Spring Harbor Laboratory SP 642033 DO 10.1101/642033 A1 Cécile Khou A1 Marco Aurelio Díaz-Salinas A1 Anaelle da Costa A1 Christophe Préhaud A1 Patricia Jeannin A1 Philippe V. Afonso A1 Marco Vignuzzi A1 Monique Lafon A1 Nathalie Pardigon YR 2019 UL http://biorxiv.org/content/early/2019/05/19/642033.abstract AB Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in South East Asia. It has been suggested that JEV gets access to the central nervous system (CNS) as a consequence of a preceding inflammatory process which leads to the blood-brain barrier (BBB) disruption and viral neuroinvasion. However, what happens at early times of JEV contact with the BBB is poorly understood. In the present work, we evaluated the ability of both a virulent and a vaccine strain of JEV (JEV RP9 and SA14-14-2, respectively) to cross an in cellulo human BBB model consisting of hCMEC/D3 human endothelial cells cultivated on permeable inserts above SK-N-SH human neuroblastoma cells. Using this system, we demonstrated that both JEV RP9 and SA14-14-2 are able to cross the BBB without disrupting it at early times post-addition. Furthermore, this BBB model was able to discriminate between the virulent RP9 and the vaccine SA14-14-2 strains, as demonstrated by the presence of almost 10 times more RP9 infectious particles that crossed the BBB than SA14-14 particles at a high MOI. Besides contributing to the understanding of early events in JEV neuroinvasion, this in cellulo BBB model represents a suitable and useful system to study the viral determinants of JEV neuroinvasiveness and the molecular mechanisms by which this flavivirus crosses the BBB at early times of neuroinvasion.