Comprehensive proteomic analysis of JC polyomavirus-infected human astrocytes and their extracellular vesicles

Microbiol Spectr. 2023 Dec 12;11(6):e0275123. doi: 10.1128/spectrum.02751-23. Epub 2023 Oct 10.

Abstract

Progressive multifocal leukoencephalopathy is a crimpling demyelinating disease of the central nervous system caused by JC polyomavirus (JCPyV). Much about JCPyV propagation in the brain remains obscure because of a lack of proper animal models to study the virus in the context of the disease, thus hampering efforts toward the development of new antiviral strategies. Here, having established a robust and representative model of JCPyV infection in human-induced pluripotent stem cell-derived astrocytes, we are able to fully characterize the effect of JCPyV on the biology of the cells and show that the proteomic signature observed for JCPyV-infected astrocytes is extended to extracellular vesicles (EVs). These data suggest that astrocyte-derived EVs found in body fluids might serve as a rich source of information relevant to JCPyV infection in the brain, opening avenues toward better understanding the pathogenesis of the virus and, ultimately, the identification of new antiviral targets.

Keywords: JCPyV; PML; astrocytes; extracellular vesicles; hiPSC; model.

MeSH terms

  • Animals
  • Antiviral Agents
  • Astrocytes
  • Extracellular Vesicles*
  • Humans
  • JC Virus* / physiology
  • Polyomavirus Infections*
  • Proteomics

Substances

  • Antiviral Agents