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Open Access 01-02-2020

Enterovirus A71 capsid protein VP1 increases blood–brain barrier permeability and virus receptor vimentin on the brain endothelial cells

Authors: Wenjing Wang, Jiandong Sun, Nan Wang, Zhixiao Sun, Qiyun Ma, Jun Li, Mingshun Zhang, Juan Xu

Published in: Journal of NeuroVirology | Issue 1/2020

Abstract

Enterovirus A71 (EV-A71) is the major cause of severe hand-foot-and-mouth diseases (HFMD), especially encephalitis and other nervous system diseases. EV-A71 capsid protein VP1 mediates virus attachment and is the important virulence factor in the EV-A71pathogenesis. In this study, we explored the roles of VP1 in the permeability of blood–brain barrier (BBB). Sera albumin, Evans blue, and dextran leaked into brain parenchyma of the 1-week-old C57BL/6J mice intracranially injected with VP1 recombinant protein. VP1 also increased the permeability of the brain endothelial cells monolayer, an in vitro BBB model. Tight junction protein claudin-5 was reduced in the brain tissues or brain endothelial cells treated with VP1. In contrast, VP1 increased the expression of virus receptor vimentin, which could be blocked with VP1 neutralization antibody. Vimentin expression in the VP1-treated brain endothelial cells was regulated by TGF-β/Smad-3 and NF-κB signal pathways. Moreover, vimentin over-expression was accompanied with compromised BBB. From these studies, we conclude that EV-A71 virus capsid protein VP1 disrupted BBB and increased virus receptor vimentin, which both may contribute to the virus entrance into brain and EV-A71 CNS infection.

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Title: Enterovirus A71 capsid protein VP1 increases blood–brain barrier permeability and virus receptor vimentin on the brain endothelial cells
Authors: Wenjing Wang
Jiandong Sun
Nan Wang
Zhixiao Sun
Qiyun Ma
Jun Li
Mingshun Zhang
Juan Xu
Publication date: 01-02-2020
Publisher: Springer International Publishing
Published in: Journal of NeuroVirology / Issue 1/2020
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-019-00800-8

At a glance: The STEP trials

Springer Medicine

Enterovirus A71 capsid protein VP1 increases blood–brain barrier permeability and virus receptor vimentin on the brain endothelial cells

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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