UMMS Affiliation

MassBiologics

Publication Date

2021-09-10

Document Type

Article

Disciplines

Immunology and Infectious Disease | Nervous System Diseases | Virus Diseases

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.

Keywords

autoimmunity, choroid plexus, demyelination, extracellular vesicle, glia, multiple sclerosis, neuroinflammation, polyomavirus

Rights and Permissions

Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

DOI of Published Version

10.3390/ijms22189809

Source

O'Hara BA, Gee GV, Haley SA, Morris-Love J, Nyblade C, Nieves C, Hanson BA, Dang X, Turner TJ, Chavin JM, Lublin A, Koralnik IJ, Atwood WJ. Teriflunomide Inhibits JCPyV Infection and Spread in Glial Cells and Choroid Plexus Epithelial Cells. Int J Mol Sci. 2021 Sep 10;22(18):9809. doi: 10.3390/ijms22189809. PMID: 34575975; PMCID: PMC8468119. Link to article on publisher's site

Journal/Book/Conference Title

International journal of molecular sciences

Related Resources

Link to Article in PubMed

PubMed ID

34575975

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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