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Abstract Details

Effect of teriflunomide on JCPyV infection in primary astrocytes and choroid plexus epithelial cells
Infectious Disease
P10 - Poster Session 10 (5:30 PM-6:30 PM)
13-017

To test the inhibition of JC polyomavirus (JCPyV) infection in glial and choroid plexus epithelial cells in vitro by teriflunomide.

Teriflunomide is an immunomodulatory drug approved for relapsing-remitting multiple sclerosis (MS). No progressive multifocal leukoencephalopathy (PML) cases attributed to teriflunomide monotherapy have been confirmed in the MS population. PML, an often-fatal neurodegenerative disease in immunosuppressed patients, is caused by JCPyV, which was found in choroid plexus epithelial cells in a patient with encephalitis, and can infect primary choroid plexus epithelial cells in vitro. The choroid plexus plays a major role in forming the blood–cerebrospinal fluid barrier and potentially in modulating viral invasion of brain parenchyma.
Immortalized primary choroid plexus epithelial (CPEpi-L) cells, and primary human astrocytes were pre-treated for one hour with 0.1 μM–2 mM teriflunomide or vehicle control, then infected with JCPyV and maintained in drug or vehicle for 5 days. Infection scoring used indirect immunofluorescent analysis of the viral gene product, VP1. Celltiter 96 Aqueous One Solution Cell Proliferation Assay (MTS) was used to evaluate cells’ tolerability to teriflunomide. A 15-day growth assay was also conducted.

Teriflunomide reduced cell proliferation of most cell lines tested, with minimal impact on cell viability. Teriflunomide at concentrations of 25 μM–100 μM significantly reduced JCPyV infection. Percent inhibition of viral infection at 5 days in primary astrocytes treated with teriflunomide at 25, 50, 75, and 100 μM was 49.6%, 59.8%, 69.0%, and 90.9%, respectively, and in CPEpi-L cells was 47.8%, 67.4%, 69.6%, and 97.8%, respectively. In cells already infected with JCPyV, teriflunomide inhibited viral spread over a 2-week period.
Teriflunomide demonstrates an in vitro effect inhibiting JCPyV. This may be related to the absence of PML cases in MS patients treated with teriflunomide.
Authors/Disclosures
Walter J. Atwood, PhD (Brown University)
PRESENTER 		No disclosure on file
No disclosure on file
Jeffrey M. Chavin, MD, FÂ鶹´«Ã½Ó³»­ (Sanofi) Dr. Chavin has received personal compensation for serving as an employee of Sanofi. Dr. Chavin has stock in Sanofi.
Ben Guikema, PhD (Sanofi Genzyme) No disclosure on file
No disclosure on file