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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Autores principales:	Song-Song Zou, Qing-Cui Zou, Wen-Jing Xiong, Ning-Yi Cui, Ke Wang, Hao-Xuan Liu, Wen-Juan Lou, Doaa Higazy, Ya-Ge Zhang, Min Cui
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	transmigration adhesion monocyte HMGB1 Japanese encephalitis virus (JEV) neuroinvasion Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d3eda9b8ada54e8c89455fd871a53deb
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spelling	oai:doaj.org-article:d3eda9b8ada54e8c89455fd871a53deb2021-11-11T14:44:30ZBrain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion2235-298810.3389/fcimb.2021.701820https://doaj.org/article/d3eda9b8ada54e8c89455fd871a53deb2021-08-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.701820/fullhttps://doaj.org/toc/2235-2988Infection 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 in vitro. 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.Song-Song ZouSong-Song ZouSong-Song ZouSong-Song ZouQing-Cui ZouQing-Cui ZouQing-Cui ZouQing-Cui ZouWen-Jing XiongWen-Jing XiongWen-Jing XiongWen-Jing XiongNing-Yi CuiNing-Yi CuiNing-Yi CuiNing-Yi CuiKe WangKe WangKe WangKe WangHao-Xuan LiuHao-Xuan LiuHao-Xuan LiuHao-Xuan LiuWen-Juan LouWen-Juan LouWen-Juan LouWen-Juan LouDoaa HigazyDoaa HigazyDoaa HigazyDoaa HigazyYa-Ge ZhangYa-Ge ZhangYa-Ge ZhangYa-Ge ZhangMin CuiMin CuiMin CuiMin CuiFrontiers Media S.A.articletransmigrationadhesionmonocyteHMGB1Japanese encephalitis virus (JEV)neuroinvasionMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	transmigration adhesion monocyte HMGB1 Japanese encephalitis virus (JEV) neuroinvasion Microbiology QR1-502
spellingShingle	transmigration adhesion monocyte HMGB1 Japanese encephalitis virus (JEV) neuroinvasion Microbiology QR1-502 Song-Song Zou Song-Song Zou Song-Song Zou Song-Song Zou Qing-Cui Zou Qing-Cui Zou Qing-Cui Zou Qing-Cui Zou Wen-Jing Xiong Wen-Jing Xiong Wen-Jing Xiong Wen-Jing Xiong Ning-Yi Cui Ning-Yi Cui Ning-Yi Cui Ning-Yi Cui Ke Wang Ke Wang Ke Wang Ke Wang Hao-Xuan Liu Hao-Xuan Liu Hao-Xuan Liu Hao-Xuan Liu Wen-Juan Lou Wen-Juan Lou Wen-Juan Lou Wen-Juan Lou Doaa Higazy Doaa Higazy Doaa Higazy Doaa Higazy Ya-Ge Zhang Ya-Ge Zhang Ya-Ge Zhang Ya-Ge Zhang Min Cui Min Cui Min Cui Min Cui Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
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 in vitro. 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.
format	article
author	Song-Song Zou Song-Song Zou Song-Song Zou Song-Song Zou Qing-Cui Zou Qing-Cui Zou Qing-Cui Zou Qing-Cui Zou Wen-Jing Xiong Wen-Jing Xiong Wen-Jing Xiong Wen-Jing Xiong Ning-Yi Cui Ning-Yi Cui Ning-Yi Cui Ning-Yi Cui Ke Wang Ke Wang Ke Wang Ke Wang Hao-Xuan Liu Hao-Xuan Liu Hao-Xuan Liu Hao-Xuan Liu Wen-Juan Lou Wen-Juan Lou Wen-Juan Lou Wen-Juan Lou Doaa Higazy Doaa Higazy Doaa Higazy Doaa Higazy Ya-Ge Zhang Ya-Ge Zhang Ya-Ge Zhang Ya-Ge Zhang Min Cui Min Cui Min Cui Min Cui
author_facet	Song-Song Zou Song-Song Zou Song-Song Zou Song-Song Zou Qing-Cui Zou Qing-Cui Zou Qing-Cui Zou Qing-Cui Zou Wen-Jing Xiong Wen-Jing Xiong Wen-Jing Xiong Wen-Jing Xiong Ning-Yi Cui Ning-Yi Cui Ning-Yi Cui Ning-Yi Cui Ke Wang Ke Wang Ke Wang Ke Wang Hao-Xuan Liu Hao-Xuan Liu Hao-Xuan Liu Hao-Xuan Liu Wen-Juan Lou Wen-Juan Lou Wen-Juan Lou Wen-Juan Lou Doaa Higazy Doaa Higazy Doaa Higazy Doaa Higazy Ya-Ge Zhang Ya-Ge Zhang Ya-Ge Zhang Ya-Ge Zhang Min Cui Min Cui Min Cui Min Cui
author_sort	Song-Song Zou
title	Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
title_short	Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
title_full	Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
title_fullStr	Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
title_full_unstemmed	Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
title_sort	brain microvascular endothelial cell-derived hmgb1 facilitates monocyte adhesion and transmigration to promote jev neuroinvasion
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d3eda9b8ada54e8c89455fd871a53deb
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Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion

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