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

Andrew N. Bubak, Cheryl Beseler, Christina N. Como, Christina M. Coughlan, Noah R. Johnson, James E. Hassell, Anna M. Burnet, Teresa Mescher, D. Scott Schmid, Colin Coleman, Ravi Mahalingam, Randall J. Cohrs, Timothy D. Boyd, Huntington Potter, Ali H. Shilleh, Holger A. Russ, Maria A. Nagel

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1284-1294
Number of pages11
JournalThe Journal of infectious diseases
Volume223
Issue number7
DOIs
StatePublished - Apr 8 2021
Externally publishedYes

Keywords

  • varicella zoster virus
  • Alzheimer disease
  • amylin
  • amyloid
  • astrocytes
  • Aβ42
  • vasculopathy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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