Microparticle-mediated VZV propagation and endothelial activation

Autor: Elena Moraitis, Paul A. Brogan, Vijeya Ganesan, Judith Breuer, Ying Hong, Cristina Venturini, Mark Turmaine, Nigel Klein, Despina Eleftheriou
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Herpesvirus 3
Human
viruses
medicine.disease_cause
Mass Spectrometry
Brain Ischemia
0302 clinical medicine
Chickenpox
Cell Movement
Cell-Derived Microparticles
Medicine
030212 general & internal medicine
Endothelial dysfunction
Child
Myofibroblasts
medicine.diagnostic_test
integumentary system
virus diseases
Stroke
medicine.anatomical_structure
Child
Preschool
Female
Myofibroblast
Adventitia
Virus Cultivation
Adolescent
In Vitro Techniques
Vascular Remodeling
Herpes Zoster
Article
Flow cytometry
Endothelial activation
03 medical and health sciences
Microscopy
Electron
Transmission
Humans
Cell Proliferation
business.industry
Cell growth
Varicella zoster virus
Endothelial Cells
Cerebral Arteries
Fibroblasts
biochemical phenomena
metabolism
and nutrition
medicine.disease
eye diseases
Cerebrovascular Disorders
Apoptosis
Immunology
Cell Transdifferentiation
Neurology (clinical)
business
030217 neurology & neurosurgery
Zdroj: Neurology
ISSN: 1526-632X
0028-3878
Popis: ObjectiveVaricella 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.MethodsHBVAFs 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.ResultsVZV-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 (p = 0.01) and controls (p = 0.007).ConclusionsVZV-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.
Databáze: OpenAIRE
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