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Journal of Virology, February 2010, p. 2150-2156, Vol. 84, No. 4
0022-538X/10/$012.00+0     doi:10.1128/JVI.01737-09
Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Leflunomide Inhibition of BK Virus Replication in Renal Tubular Epithelial Cells {triangledown}

Eva Bernhoff,1,2 Garth D. Tylden,1 Lars J. Kjerpeseth,1 Tore J. Gutteberg,1,2 Hans H. Hirsch,3,4 and Christine H. Rinaldo1*

Department of Microbiology and Infection Control, University Hospital of North Norway,1 Department of Microbiology and Virology, Institute for Medical Microbiology, University of Tromsø, Tromsø, Norway,2 Transplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel,3 Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland4

Received 18 August 2009/ Accepted 23 November 2009

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 µg/ml reduced the extracellular BKV load by 90% (IC90) 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.

* Corresponding author. Mailing address: Department of Microbiology and Infection Control, University Hospital of North Norway, P.O. Box 56, N-9038 Tromsø, Norway. Phone: 4777627335. Fax: 4777627015. E-mail: christine.rinaldo{at}unn.no

{triangledown} Published ahead of print on 2 December 2009.

Journal of Virology, February 2010, p. 2150-2156, Vol. 84, No. 4
0022-538X/10/$012.00+0     doi:10.1128/JVI.01737-09
Copyright © 2010, American Society for Microbiology. All Rights Reserved.





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