Teriflunomide inhibits jcpyv infection and spread in glial cells and choroid plexus epithelial cells

Bethany A. O’hara, Gretchen V. Gee, Sheila A. Haley, Jenna Morris-Love, Charlotte Nyblade, Chris Nieves, Barbara A. Hanson, Xin Dang, Timothy J. Turner, Jeffrey M. Chavin, Alex Lublin, Igor J. Koralnik, Walter J. Atwood*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Several classes of immunomodulators are used for treating relapsing-remitting multiple sclerosis (RRMS). Most of these disease-modifying therapies, except teriflunomide, carry the risk of progressive multifocal leukoencephalopathy (PML), a severely debilitating, often fatal virus-induced demyelinating disease. Because teriflunomide has been shown to have antiviral activity against DNA viruses, we investigated whether treatment of cells with teriflunomide inhibits infection and spread of JC polyomavirus (JCPyV), the causative agent of PML. Treatment of choroid plexus epithelial cells and astrocytes with teriflunomide reduced JCPyV infection and spread. We also used droplet digital PCR to quantify JCPyV DNA associated with extracellular vesicles isolated from RRMS patients. We detected JCPyV DNA in all patients with confirmed PML diagnosis (n = 2), and in six natalizumab-treated (n = 12), two teriflunomide-treated (n = 7), and two nonimmunomodulated (n = 2) patients. Of the 21 patients, 12 (57%) had detectable JCPyV in either plasma or serum. CSF was uniformly negative for JCPyV. Isolation of extracellular vesicles did not increase the level of detection of JCPyV DNA versus bulk unprocessed biofluid. Overall, our study demonstrated an effect of teriflunomide inhibiting JCPyV infection and spread in glial and choroid plexus epithelial cells. Larger studies using patient samples are needed to correlate these in vitro findings with patient data.

Original languageEnglish (US)
Article number9809
JournalInternational journal of molecular sciences
Volume22
Issue number18
DOIs
StatePublished - Sep 2021

Keywords

  • Autoimmunity
  • Choroid plexus
  • Demyelination
  • Extracellular vesicle
  • Glia
  • Multiple sclerosis
  • Neuroinflammation
  • Polyomavirus

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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