Department of Microbiology and Infection Control, University Hospital of North Norway, P.O. Box 56, N-9038 Tromsø, Norway.
J Virol. 2010 Feb;84(4):2150-6. doi: 10.1128/JVI.01737-09. Epub 2009 Dec 2.
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.
免疫调节药物来氟米特常用于治疗多瘤病毒相关性肾病，但抗病毒机制尚不清楚。我们描述了活性代谢产物 A771726（LEF-A）对人肾小管上皮细胞中多瘤病毒 BK（BKV）生命周期的影响。LEF-A 在 10μg/ml 时将细胞外 BKV 载量减少了 90%（IC90），但对宿主有明显的细胞抑制作用。BKV 基因组复制、晚期蛋白表达以及病毒颗粒组装和释放均受到抑制，核复制结构也受到明显破坏。加入尿嘧啶后，宿主细胞和抗病毒作用均得到了很大程度的逆转，表明非特异性嘧啶耗竭是来氟米特抗 BKV 的主要机制。
