Invasion of a murine in vitro blood-brain barrier co-culture model by dengue virus serotypes 1 to 4
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The blood-brain barrier (BBB) is a physical barrier that restricts the passage of cells and molecules as well as pathogens into the central nervous system (CNS). Some viruses enter the CNS by disrupting the BBB, while others can reach the CNS without altering the integrity of the BBB. Even though dengue virus (DENV) is not a distinctive neurotropic virus, the virus is considered to be one of the leading causes of neurological manifestations. In this study, we found that DENV is able to compromise the integrity of a murine in vitro blood-brain barrier (BBB) model, resulting in hyperpermeability, as shown by a significant increase in sucrose and albumin permeability. Infection of brain endothelial cells (ECs) was facilitated by the presence 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 was observed, leading to a significant decrease in tight-junction protein expression and peripheral localization, which contributed to the changes in BBB permeability. In conclusion, the hyperpermeability and breaching mechanism of BBB by DENV are primarily due to direct consequences of viral infection of ECs, as shown in this in vitro study.
This work is supported by Universiti Brunei Darussalam. Idris F is a recipient of the Graduate Research Scholarships (GRS), Universiti Brunei Darussalam.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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