Japanese encephalitis virus-associated human microglia induce cell death of human microvascular endothelial cells in receptor-independent infection
Year: 2025
Type: article
Abstract: Introduction: The neurotropic virus Japanese encephalitis virus invades the human central nervous system, inducing neuroinflammation and further disruption of the blood-brain barrier. JEV interacts with various cell types of the blood-brain barrier including the endothelial cells. The present work aims to investigate impact of receptor-dependent and independent infection of human microvascular endothelial cells by Japanese encephalitis virus. Methods: Receptor-dependent infection was achieved using cell-free virus while receptor-independent infection was by co-culture of microvascular endothelial cells with virus-associated microglia. Results: CL1 axis was inefficient in blocking virus rescue and protecting endothelial cell from cell death, transcriptomics analysis identified Tumour Necrosis Factor-related apoptosis inducing ligand and receptors as potential key player leading to endothelial cell death. Discussion: Overall, our findings demonstrate that human microvascular endothelial cells supply virus propagation and Japanese encephalitis virus-associated microglia greatly contribute to endothelial cell death, an important component of the blood brain barrier integrity. Importantly, Tumour Necrosis Factor-related apoptosis inducing ligand and receptors represents a promising therapeutic target preventing microvascular endothelial cell death after neuroinvasion.
Authors: Isabelle Fellay, Pauline Blanc, Alexey Larionov, Léa Schlunke, Luis Filgueira, Nils Lannes
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Award: G5017347903
OpenAlex ID: W4410040706