Division of Transplant Pathology, University of Pittsburgh, Department of Pathology, E737 UPMC-Montefiore Hospital, 3459 Fifth Ave, Pittsburgh, PA 15213, USA.
Am J Clin Pathol. 2010 Dec;134(6):916-20. doi: 10.1309/AJCP7JYHJN1PGQVC.
Our objective was to determine whether quantitative polymerase chain reaction (PCR) can be used to measure the effect of tyrosine kinase (TK) inhibition on polyomavirus BK (BKV) replication. The BKV was grown in a cell culture system. The rate of viral replication in the presence or absence of the drug being tested was assessed by amplifying the viral genome using primers directed against the viral capsid 1 protein. Dasatinib, erlotinib, gefitinib, imatinib, sunitinib, and sorafenib all showed antiviral activity at micromolar concentrations. The 50% effective concentration for erlotinib and sorafenib was within blood concentrations readily achieved in human subjects. Quantitative PCR is a convenient method for viral drug sensitivity testing for slow-growing viruses that do not readily produce cytopathic effect. TK inhibitors deserve further consideration as a potential therapeutic option for BKV-associated nephropathy and hemorrhagic cystitis.
我们的目的是确定定量聚合酶链反应（PCR）是否可用于测量酪氨酸激酶（TK）抑制对多瘤病毒 BK（BKV）复制的影响。BKV 在细胞培养系统中生长。通过使用针对病毒衣壳 1 蛋白的引物扩增病毒基因组来评估存在或不存在待测试药物时的病毒复制率。达沙替尼、厄洛替尼、吉非替尼、伊马替尼、舒尼替尼和索拉非尼在微摩尔浓度下均显示出抗病毒活性。厄洛替尼和索拉非尼的 50%有效浓度在人类受试者中容易达到的血液浓度范围内。定量 PCR 是一种用于检测生长缓慢且不易产生细胞病变效应的病毒的药物敏感性的便捷方法。TK 抑制剂值得进一步考虑作为 BKV 相关性肾病和出血性膀胱炎的潜在治疗选择。
