Amylin, Aβ42, and Amyloid in Varicella Zoster Virus Vasculopathy Cerebrospinal Fluid and Infected Vascular Cells.

Autor:	Bubak AN; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA., Beseler C; Department of Psychology, Colorado State University, Fort Collins, Colorado, USA., Como CN; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA., Coughlan CM; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA., Johnson NR; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA., Hassell JE; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA., Burnet AM; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA., Mescher T; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA., Schmid DS; Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA., Coleman C; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA., Mahalingam R; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA., Cohrs RJ; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA.; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA., Boyd TD; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA., Potter H; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA., Shilleh AH; Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, Colorado, USA., Russ HA; Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, Colorado, USA., Nagel MA; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA.; Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2021 Apr 08; Vol. 223 (7), pp. 1284-1294.
DOI:	10.1093/infdis/jiaa513
Abstrakt:	Background: Varicella zoster virus (VZV) vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system infection produces amyloid. Methods: Aβ peptides, amylin, and amyloid were measured in cerebrospinal fluid (CSF) from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with small interfering RNA and viral complementary DNA (cDNA) was quantitated. Results: Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA. Conclusions: VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin. (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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