Leflunomide inhibition of BK virus replication in renal tubular epithelial cells

Bernhoff, Eva and Tylden, Garth D. and Kjerpeseth, Lars J. and Gutteberg, Tore J. and Hirsch, Hans H. and Rinaldo, Christine H.. (2010) Leflunomide inhibition of BK virus replication in renal tubular epithelial cells. Journal of virology, Vol. 84, H. 4. pp. 2150-2156.

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Official URL: http://edoc.unibas.ch/dok/A6005128

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The immunomodulatory drug leflunomide is frequently used for treating polyomavirus-associated nephropathy, yet its antiviral mechanism is unclear. We characterized the effects of the active leflunomide metabolite A771726 (LEF-A) on the polyomavirus BK (BKV) life cycle in human renal tubular epithelial cells. LEF-A at 10 microg/ml reduced the extracellular BKV load by 90% (IC(90)) but with significant host cytostatic effects. BKV genome replication, late protein expression, and virion assembly and release were inhibited with visible disruption of the nuclear replication architecture. Both host cell and antiviral effects were largely reversed by uridine addition, implicating nonspecific pyrimidine depletion as the major anti-BKV mechanism of leflunomide.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Transplantation Virology (Hirsch)
UniBasel Contributors:Hirsch, Hans H.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Microbiology
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:22
Deposited On:24 May 2013 09:05

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