Leflunomide Inhibition of BK Virus Replication in Renal Tubular Epithelial Cells

被引：92

作者：

Bernhoff, Eva ^{[1
,2
]}

Tylden, Garth D. ^{[1
]}

Kjerpeseth, Lars J. ^{[1
]}

Gutteberg, Tore J. ^{[1
,2
]}

Hirsch, Hans H. ^{[3
,4
]}

Rinaldo, Christine H. ^{[1
]}

机构：

[1] Univ Hosp N Norway, Dept Microbiol & Infect Control, N-9038 Tromso, Norway

[2] Univ Tromso, Inst Med Microbiol, Dept Microbiol & Virol, Tromso, Norway

[3] Univ Basel, Inst Med Microbiol, Dept Biomedicine, Basel, Switzerland

[4] Univ Basel Hosp, CH-4031 Basel, Switzerland

来源：

JOURNAL OF VIROLOGY | 2010年 / 84卷 / 04期

关键词：

POLYOMAVIRUS-ASSOCIATED NEPHROPATHY; IN-VITRO; IMMUNOSUPPRESSIVE AGENT; INFECTION; VIVO; QUANTITATION; METABOLITE; CLEARANCE; CIDOFOVIR; TYPE-1;

D O I：

10.1128/JVI.01737-09

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 mu g/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.

引用

页码：2150 / 2156

页数：7

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