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J Virol. 2010 Feb;84(4):2150-6. doi: 10.1128/JVI.01737-09. Epub 2009 Dec 2.

Leflunomide inhibition of BK virus replication in renal tubular epithelial cells.

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  • 1Department of Microbiology and Infection Control, University Hospital of North Norway, P.O. Box 56, N-9038 Tromsø, Norway.

Abstract

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.

PMID:
19955306
[PubMed - indexed for MEDLINE]
PMCID:
PMC2812362
Free PMC Article

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