Journal of Virology · 2009 · 107 citations · 38 references
MedicineNephrologyPharmacologyMolecular PharmacologyMolecular VirologyVirologyAntiviral AgentsAntiviral PharmacologyAntiviral TherapyOncogenic VirusesRenal DiseaseRenal PharmacologyAntiviral TherapeuticsAntiviral TreatmentGenome ReplicationPolyomavirus NephropathyPolyomavirus-associated NephropathyViral Replication InhibitionViral Replication InhibitorsVirus Replication Inhibition
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.
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Leflunomide for Polyomavirus Type BK Nephropathy
James W. Williams, Basit Javaid, Predeep V. Kadambi et al. · New England Journal of Medicine · 2005 · 238 citations · Full text
Treatment of Renal Allograft Polyoma BK Virus Infection with Leflunomide
Michelle A. Josephson, Daniel L. Gillen, Basit Javaid et al. · Transplantation · 2006 · 225 citations