Japanese encephalitis virus infection increases blood-brain barrier permeability in a human model by inducing a strong pro-inflammatory endothelial response

Published: 9 April 2018| Version 1 | DOI: 10.17632/hzzbg2z7bm.1
Adjanie Patabendige, Benedict Michael, Alister Craig, Tom Solomon


Japanese encephalitis (JE) continues to be the most important cause of viral encephalitis globally. Following the bite of an infected mosquito, Japanese encephalitis virus (JEV) replicates in the skin and local lymph nodes before crossing the blood-brain barrier (BBB - the physiological barrier that protects the brain from blood-borne toxins and pathogens) to enter the brain. Little is known about the exact mechanisms of JEV entry across the BBB into the brain. Data from clinical studies suggest the BBB is disrupted in JE, leading to brain swelling, and that a strong pro-inflammatory cytokine response may be important in this. To better understand the disease mechanisms, we established a BBB model using human brain cells. We demonstrated that JEV infection of the BBB triggers a host inflammatory response, which impairs virus production but causes disruption of the BBB, thus allowing viral entry into the brain. Our data showed that the corticosteroid drug dexamethasone, which is sometimes used to treat JE in Asia, reduces the inflammatory response and the BBB disruption. This data set supporting the studies described in the related article provides new insights into the complex interactions between the BBB and JEV, and the potential role of anti- inflammatory treatment.



Blood-Brain Barrier, Corticosteroid, Cytokine Response, Viral Encephalitis, In Vitro Study