LSTM Home > LSTM Research > LSTM Online Archive

Brain microvascular endothelial-astrocyte cell responses following Japanese encephalitis virus infection in an in vitro human blood-brain barrier model.

Patabendige, Adjanie, Michael, Benedict D, Craig, Alister ORCID: and Solomon, Tom (2018) 'Brain microvascular endothelial-astrocyte cell responses following Japanese encephalitis virus infection in an in vitro human blood-brain barrier model.'. Molecular and Cellular Neurosciences, Vol 89, pp. 60-70.

Molecular and Cellular Neuroscience_Brain microvascular endothelial-astrocyte cell responses following Japanese encephalitis virus infection.pdf - Published Version
Available under License Creative Commons Attribution.

Download (3MB) | Preview


Japanese encephalitis virus (JEV) remains a leading cause of encephalitis, globally, which continues to grow in importance despite the availability of vaccines. Viral entry into the brain can occur via the blood-brain barrier (BBB), and inflammation at the BBB is a common final pathway in many brain infections. However, the role of the BBB during JEV infection and the contribution of the endothelial and astrocytic cell inflammation in facilitating virus entry into the brain are incompletely understood. We established a BBB model using human brain endothelial cells (HBECs) and human astrocytes. HBECs are polarised, and therefore the model was inoculated by JEV from the apical side to simulate the in vivo situation. The effects of JEV on the BBB permeability and release of inflammatory mediators from both apical and basolateral sides, representing the blood and the brain side respectively were investigated. JEV infected HBECs with limited active virus production, before crossing the BBB and infecting astrocytes. Control of JEV production by HBECs was associated with a significant increase in permeability, and with elevation of many host mediators, including cytokines, chemokines, cellular adhesion molecules, and matrix metalloproteases. When compared to the controls, significantly higher amounts of mediators were released from the apical side as opposed to the basolateral side. The increased release of mediators over time also correlated with increased BBB permeability. Treatment with dexamethasone led to a significant reduction in the release of interleukin 6 (IL6), C-C motif chemokine ligand 5 (CCL5) and C-X-C motif chemokine ligand 10 (CXCL10) from the apical side with a reduction in BBB disruption and no change in JEV replication. The results are consistent with the hypothesis that JEV infection of the BBB triggers the production of a range of host mediators from both endothelial cells and astrocytes, which control JEV production but disrupt BBB integrity thus allowing virus entry into the brain. Dexamethasone treatment controlled the host response and limited BBB disruption in the model without increasing JEV production, supporting a re-investigation of its use therapeutically.

Item Type: Article
Subjects: WL Nervous System > WL 100 General works
WL Nervous System > WL 20 Research (General)
WL Nervous System > WL 200 Meninges. Blood-brain barrier
WL Nervous System > WL 300 General works (Include works on brain alone)
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):
SWORD Depositor: JISC Pubrouter
Depositing User: Stacy Murtagh
Date Deposited: 25 Apr 2018 11:44
Last Modified: 17 Jul 2019 14:15


View details

Actions (login required)

Edit Item Edit Item