Microparticle-mediated VZV propagation and endothelial activation: Mechanism of VZV vasculopathy.
Adolescent
Adventitia
Cell Movement
Cell Proliferation
Cell Transdifferentiation
Cell-Derived Microparticles
/ ultrastructure
Cerebral Arteries
Cerebrovascular Disorders
/ physiopathology
Child
Child, Preschool
Endothelial Cells
Female
Fibroblasts
/ physiology
Herpesvirus 3, Human
Humans
In Vitro Techniques
Male
Mass Spectrometry
Microscopy, Electron, Transmission
Myofibroblasts
/ physiology
Stroke
/ physiopathology
Vascular Remodeling
Virus Cultivation
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
04 02 2020
04 02 2020
Historique:
received:
14
03
2019
accepted:
20
08
2019
pubmed:
2
1
2020
medline:
19
5
2020
entrez:
2
1
2020
Statut:
ppublish
Résumé
Varicella zoster virus (VZV) can spread anterogradely and infect cerebral arteries causing VZV vasculopathy and arterial ischemic stroke. In this study, we tested the hypothesis that virus-infected cerebrovascular fibroblasts undergo phenotypic changes that promote vascular remodeling and facilitate virus transmission in an in vitro model of VZV vasculopathy. The aims of this project were therefore to examine the changes that virus-infected human brain adventitial vascular fibroblasts (HBVAFs) undergo in an in vitro model of VZV vasculopathy and to identify disease biomarkers relating to VZV-related vasculopathy. HBVAFs were infected with VZV, and their ability to migrate, proliferate, transdifferentiate, and interact with endothelial cells was studied with flow cytometry. Microparticles (MPs) released from these cells were isolated and imaged with transmission electron microscopy, and their protein content was analyzed with mass spectrometry. Circulating MP profiles were also studied in children with VZV and non-VZV vasculopathy and compared with controls. VZV-infected HBVAFs transdifferentiated into myofibroblasts with enhanced proliferative and migratory capacity. Interaction of VZV-infected HBVAFs with endothelial cells resulted in endothelial dysfunction. These effects were, in part, mediated by the release of MPs from VZV-infected HBVAFs. These MPs contained VZV virions that could transmit VZV to neighboring cells, highlighting a novel model of VZV cell-to-cell viral dissemination. MPs positive for VZV were significantly higher in children with VZV-related vasculopathy compared to children with non-VZV vasculopathy ( VZV-infected HBVAFs promote vascular remodeling and facilitate virus transmission. These effects were mediated by the release of apoptotic MPs that could transmit VZV infection to neighboring cells through a Trojan horse means of productive viral infection. VZV+ MPs may represent a disease biomarker worthy of further study.
Identifiants
pubmed: 31892634
pii: WNL.0000000000008885
doi: 10.1212/WNL.0000000000008885
pmc: PMC7080289
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e474-e480Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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