TY - JOUR
KW - brain microvascular networks
KW - endothelial dysfunction
KW - flavivirus non-structural protein 1
KW - microfluidic chips
AU - Monika Rajput
AU - Yen-Ting Tung
AU - Yu-Chi Chen
AU - Min Jae Song
AU - Marc Ferrer
AU - Emily M. Lee
AB - Flaviviruses can lead to severe neurotropic-encephalitic pathology, for which the viral nonstructural protein 1 (NS1) plays a major role. 2D in vitro cellular systems and animal models are currently used to investigate the effects of flavivirus NS1 in the brain-blood barrier do not fully capture pathogenesis and drug responses seen in humans. Here is reported the development of a perfusable human brain microvascular network-on-a-chip (BMVasChip) model which incorporates brain endothelial cells and pericytes and recapitulates the cellular organization and expression of brain blood barrier-specific markers, including intracellular junction proteins. This BMVasChip model is used to investigate vasculopathy caused by exposure to a panel of flavivirus NS1 proteins, including Japanese encephalitis (JEV), West Nile (WNV), and dengue virus (DENV) NS1 proteins. The BMVasChip platform is able to demonstrate flavivirus NS1-induced pathophysiological phenotypes in the BMVasChip, including early and late endothelial activation and dysfunction features such as loss of barrier integrity, morphological features, and production of pro-inflammatory markers in a virus, dose, and time-dependent manner. In summary, the BMVasChip model recapitulates key features of endothelial dysfunction, potentially reflecting NS1's role in viral pathogenesis and providing targets for antiviral therapeutics and vaccine development.
BT - Advanced Functional Materials
DO - 10.1002/adfm.202504476
IS - n/a
LA - en
N2 - Flaviviruses can lead to severe neurotropic-encephalitic pathology, for which the viral nonstructural protein 1 (NS1) plays a major role. 2D in vitro cellular systems and animal models are currently used to investigate the effects of flavivirus NS1 in the brain-blood barrier do not fully capture pathogenesis and drug responses seen in humans. Here is reported the development of a perfusable human brain microvascular network-on-a-chip (BMVasChip) model which incorporates brain endothelial cells and pericytes and recapitulates the cellular organization and expression of brain blood barrier-specific markers, including intracellular junction proteins. This BMVasChip model is used to investigate vasculopathy caused by exposure to a panel of flavivirus NS1 proteins, including Japanese encephalitis (JEV), West Nile (WNV), and dengue virus (DENV) NS1 proteins. The BMVasChip platform is able to demonstrate flavivirus NS1-induced pathophysiological phenotypes in the BMVasChip, including early and late endothelial activation and dysfunction features such as loss of barrier integrity, morphological features, and production of pro-inflammatory markers in a virus, dose, and time-dependent manner. In summary, the BMVasChip model recapitulates key features of endothelial dysfunction, potentially reflecting NS1's role in viral pathogenesis and providing targets for antiviral therapeutics and vaccine development.
EP - e04476
T2 - Advanced Functional Materials
TI - Perfusable Brain Microvascular Network-On-Chip Model to Study Flavivirus NS1-Induced Endothelial Dysfunction
UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/adfm.202504476
VL - n/a
Y2 - 2025-09-22
SN - 1616-3028
ER -