Leflunomide Inhibition of BK Virus Replication in Renal Tubular Epithelial Cells-Reference-Cited by-同舟云学术

Leflunomide Inhibition of BK Virus Replication in Renal Tubular Epithelial Cells

Published:2010-02-15 Issue:4 Volume:84 Page:2150-2156
ISSN:0022-538X
Container-title:Journal of Virology
language:en
Short-container-title:J Virol

Author:

Bernhoff Eva¹²,Tylden Garth D.¹,Kjerpeseth Lars J.¹,Gutteberg Tore J.¹²,Hirsch Hans H.³⁴,Rinaldo Christine H.¹

Affiliation:

1. Department of Microbiology and Infection Control, University Hospital of North Norway

2. Department of Microbiology and Virology, Institute for Medical Microbiology, University of Tromsø, Tromsø, Norway

3. Transplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel

4. Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland

Abstract

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% (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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Link

https://journals.asm.org/doi/pdf/10.1128/JVI.01737-09

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