Teriflunomide Inhibits JCPyV Infection and Spread in Glial Cells and Choroid Plexus Epithelial Cells
Authors
O'Hara, Bethany A.Gee, Gretchen V.
Haley, Sheila A.
Morris-Love, Jenna
Nyblade, Charlotte
Nieves, Chris
Hanson, Barbara A.
Dang, Xin
Turner, Timothy J.
Chavin, Jeffrey M.
Lublin, Alex
Koralnik, Igor J.
Atwood, Walter J.
UMass Chan Affiliations
MassBiologicsDocument Type
Journal ArticlePublication Date
2021-09-10Keywords
autoimmunitychoroid plexus
demyelination
extracellular vesicle
glia
multiple sclerosis
neuroinflammation
polyomavirus
Immunology and Infectious Disease
Nervous System Diseases
Virus Diseases
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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.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
DOI
10.3390/ijms22189809Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42706PubMed ID
34575975Related Resources
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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/).Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.3390/ijms22189809
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Except where otherwise noted, this item's license is described as 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/).