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http://purl.uniprot.org/citations/37832655http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37832655http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

EV71 (Enterovirus 71) is a major causative agent of the outbreaks of HFMD (hand, foot, and mouth disease), which is associated with neurological damage caused by permeability disruption of BBB (blood-brain barrier). HMGB1 (high-mobility group box 1) is a widely expressed nuclear protein that triggers host inflammatory responses. Our work aimed to explore the function of HMGB1 in EV71 infection and its contributions to EV71-related BBB damage.

Methods

HeLa cells, HT-29 cells and AG6 mice were used to explore the translocation of HMGB1 in EV71 infection in vitro and in vivo. The roles of released HMGB1 on EV71 replication and associated inflammatory cytokines were investigated using recombinant HMGB1 in HeLa cells. The mechanisms of released HMGB1 in EV71-induced BBB injury were explored using recombinant HMGB1 and anti-HMGB1 neutralizing antibodies in monolayer HCMECs (immortalized human brain microvascular endothelial cells) and AG6 mice brain.

Results

EV71 induced HMGB1 nucleocytoplasmic translocation and extracellular release in vitro and in vivo. Released HMGB1 acted as an inflammatory mediator in EV71 infection rather than affecting viral replication in vitro. Released HMGB1 disrupted BBB integrity by enhancing VE-cadherin phosphorylation at tyrosine 685 in HCMECs, and reducing total VE-cadherin levels in HCMECs and AG6 mice in EV71 infection. And released HMGB1 induced an increase in activated astrocytes. Neutralization of HMGB1 reversed the increased endothelial hyperpermeability and phosphorylation of VE-cadherin in HCMECs.

Conclusion

The inflammatory mediator HMGB1 released by EV71 exacerbated BBB disruption by enhancing VE-cadherin phosphorylation, which in turn aggravated EV71-induced neuroinflammation."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.org/dc/terms/identifier"doi:10.1016/j.virusres.2023.199240"xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"Chen D."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"Jiang N."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"Cai Y."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"Liu Y."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"Tian X."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"Wu J."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"Zhang F."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"Wu Z."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"Yang E."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"Zheng N."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"You Q."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/author"Lyu R."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/name"Virus Res"xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/pages"199240"xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/title"HMGB1 Release Induced by EV71 Infection Exacerbates Blood-Brain Barrier Disruption via VE-cadherin Phosphorylation."xsd:string
http://purl.uniprot.org/citations/37832655http://purl.uniprot.org/core/volume"338"xsd:string
http://purl.uniprot.org/citations/37832655http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/37832655
http://purl.uniprot.org/citations/37832655http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/37832655
http://purl.uniprot.org/uniprot/#_A0A286R9D9-mappedCitation-37832655http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37832655
http://purl.uniprot.org/uniprot/#_A0A286R9F1-mappedCitation-37832655http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37832655
http://purl.uniprot.org/uniprot/#_B7Z965-mappedCitation-37832655http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37832655
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