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 |
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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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