Leflunomide Inhibition of BK Virus Replication in Renal Tubular Epithelial Cells
- Bernhoff, Eva Department of Microbiology and Virology, Institute for Medical Microbiology, University of Tromsø, Tromsø, Norway
- Tylden, Garth D. Department of Microbiology and Infection Control, University Hospital of North Norway
- Kjerpeseth, Lars J. Department of Microbiology and Infection Control, University Hospital of North Norway
- Gutteberg, Tore J. Department of Microbiology and Virology, Institute for Medical Microbiology, University of Tromsø, Tromsø, Norway
- Hirsch, Hans H. Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
- Rinaldo, Christine H. Department of Microbiology and Infection Control, University Hospital of North Norway
Published in:
- Journal of Virology. - American Society for Microbiology. - 2009, vol. 84, no. 4, p. 2150-2156
English
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 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.
- Language
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- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1128/jvi.01737-09
- ISSN 0022-538X
- Persistent URL
- https://sonar.ch/global/documents/51268
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