Varicella-Zoster Virus Infection of Primary Human Spinal Astrocytes Produces Intracellular Amylin, Amyloid-β, and an Amyloidogenic Extracellular Environment

J Infect Dis. 2020 Mar 16;221(7):1088-1097. doi: 10.1093/infdis/jiz560.


Background: Herpes zoster is linked to amyloid-associated diseases, including dementia, macular degeneration, and diabetes mellitus, in epidemiological studies. Thus, we examined whether varicella-zoster virus (VZV)-infected cells produce amyloid.

Methods: Production of intracellular amyloidogenic proteins (amylin, amyloid precursor protein [APP], and amyloid-β [Aβ]) and amyloid, as well as extracellular amylin, Aβ, and amyloid, was compared between mock- and VZV-infected quiescent primary human spinal astrocytes (qHA-sps). The ability of supernatant from infected cells to induce amylin or Aβ42 aggregation was quantitated. Finally, the amyloidogenic activity of viral peptides was examined.

Results: VZV-infected qHA-sps, but not mock-infected qHA-sps, contained intracellular amylin, APP, and/or Aβ, and amyloid. No differences in extracellular amylin, Aβ40, or Aβ42 were detected, yet only supernatant from VZV-infected cells induced amylin aggregation and, to a lesser extent, Aβ42 aggregation into amyloid fibrils. VZV glycoprotein B (gB) peptides assembled into fibrils and catalyzed amylin and Aβ42 aggregation.

Conclusions: VZV-infected qHA-sps produced intracellular amyloid and their extracellular environment promoted aggregation of cellular peptides into amyloid fibrils that may be due, in part, to VZV gB peptides. These findings suggest that together with host and other environmental factors, VZV infection may increase the toxic amyloid burden and contribute to amyloid-associated disease progression.

Keywords: Alzheimer disease; Aβ42; amylin; amyloid; astrocytes; varicella-zoster virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / pharmacology
  • Amyloid beta-Peptides* / chemistry
  • Amyloid beta-Peptides* / metabolism
  • Antiviral Agents / pharmacology
  • Astrocytes* / drug effects
  • Astrocytes* / metabolism
  • Astrocytes* / virology
  • Cells, Cultured
  • Extracellular Space / metabolism
  • Humans
  • Intracellular Space / metabolism
  • Islet Amyloid Polypeptide* / chemistry
  • Islet Amyloid Polypeptide* / metabolism
  • Varicella Zoster Virus Infection / metabolism*
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / metabolism


  • Amyloid beta-Peptides
  • Antiviral Agents
  • Islet Amyloid Polypeptide
  • Viral Envelope Proteins
  • glycoprotein B, varicella-zoster virus
  • Acyclovir