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Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion

Infection with Japanese encephalitis virus (JEV) induces high morbidity and mortality, including potentially permanent neurological sequelae. However, the mechanisms by which viruses cross the blood-brain barrier (BBB) and invade into the central nervous system (CNS) remain unclear. Here, we show th...

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Published in:Frontiers in cellular and infection microbiology 2021-08, Vol.11, p.701820-701820
Main Authors: Zou, Song-Song, Zou, Qing-Cui, Xiong, Wen-Jing, Cui, Ning-Yi, Wang, Ke, Liu, Hao-Xuan, Lou, Wen-Juan, Higazy, Doaa, Zhang, Ya-Ge, Cui, Min
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creator Zou, Song-Song
Zou, Qing-Cui
Xiong, Wen-Jing
Cui, Ning-Yi
Wang, Ke
Liu, Hao-Xuan
Lou, Wen-Juan
Higazy, Doaa
Zhang, Ya-Ge
Cui, Min
description Infection with Japanese encephalitis virus (JEV) induces high morbidity and mortality, including potentially permanent neurological sequelae. However, the mechanisms by which viruses cross the blood-brain barrier (BBB) and invade into the central nervous system (CNS) remain unclear. Here, we show that extracellular HMGB1 facilitates immune cell transmigration. Furthermore, the migration of immune cells into the CNS dramatically increases during JEV infection which may enhance viral clearance, but paradoxically expedite the onset of Japanese encephalitis (JE). In this study, brain microvascular endothelial cells (BMECs) were utilized for the detection of HMGB1 release, and leucocyte, adhesion, and the integrity of the BBB . Genetically modified JEV-expressing EGFP (EGFP-JEV) and the BBB model were established to trace JEV-infected immune cell transmigration, which mimics the process of viral neuroinfection. We find that JEV causes HMGB1 release from BMECs while increasing adhesion molecules. Recombinant HMGB1 enhances leukocyte-endothelium adhesion, facilitating JEV-infected monocyte transmigration across endothelia. Thus, JEV successfully utilizes infected monocytes to spread into the brain, expanding inside of the brain, and leading to the acceleration of JE onset, which was facilitated by HMGB1. HMGB1-promoted monocyte transmigration may represent the mechanism of JEV neuroinvasion, revealing potential therapeutic targets.
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subjects adhesion
Animals
Brain
Cell Adhesion
Cell Movement
Cellular and Infection Microbiology
Disease Models, Animal
Encephalitis Virus, Japanese - pathogenicity
Encephalitis, Japanese - immunology
Endothelial Cells
Endothelium
Female
HMGB1
HMGB1 Protein
Japanese encephalitis virus (JEV)
Mice
Mice, Inbred C57BL
monocyte
Monocytes - cytology
neuroinvasion
transmigration
Virus Internalization
title Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
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