Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, 1200 Newell Drive, Gainesville, FL 32610, United States.
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, 1200 Newell Drive, Gainesville, FL 32610, United States.
Antiviral Res. 2018 Apr;152:68-75. doi: 10.1016/j.antiviral.2018.02.012. Epub 2018 Feb 16.
The ability of antiviral polyamides (AVP) to act upon polyomaviruses (PyV) was evaluated. Initial studies found that a single treatment of AVP protected SV40-infected BSC-1 cells from cytopathic effect (CPE) for as long as 11 days p.i.. AVP substantially suppressed SV40 genome copy numbers over the duration of the experiment. Immunofluorescence analysis of ataxia-telangiectasia mutated (ATM) activation and large T antigen (LTag) expression clearly demonstrated that AVP treatment at day 1 p.i. delayed the onset of productive SV40 replication by approximately 3 days, and substantially limited the infection relative to vehicle-treated controls. AVP dose-response experiments recorded IC50s in the low nM range that were similar to IC50s previously reported for HPV16. The ability of AVPs to act on BKPyV was next examined. Again, IC50s in the low nM range were obtained with the exception of an AVP (PA1) that gave an IC50 of 437 nM against the BKPyV Dunlop strain. The Mre11 inhibitor Mirin substantially reduced the AVP IC50 against SV40 demonstrating that Mre11 protects PyV genomes from AVP action as previously shown for HPV. Together these experiments show that AVPs are potent antiviral agents for PyV that act via a mechanism with similarities to that found for HPV. The results demonstrate that AVPs are useful tools for controlling and studying PyV biology. The potential use of these agents against BKPyV and other PyV pathogens also has clinical implications.
抗病毒多聚体（AVP）对多瘤病毒（PyV）的作用能力进行了评估。初步研究发现，AVP 单次处理可使 SV40 感染的 BSC-1 细胞免受细胞病变效应（CPE）长达 11 天。在整个实验过程中，AVP 大大抑制了 SV40 基因组拷贝数。用 ATM 激活和大 T 抗原（LTag）表达的免疫荧光分析清楚地表明，AVP 治疗在感染后第 1 天延迟了 SV40 复制的开始时间，大约为 3 天，并且与载体处理的对照相比，大大限制了感染。AVP 剂量反应实验记录的 IC50 在低 nM 范围内，与之前报道的 HPV16 的 IC50 相似。接下来检查了 AVPs 对 BKPyV 的作用能力。同样，除了 AVP（PA1）对 BKPyV Dunlop 株的 IC50 为 437 nM 外，也获得了低 nM 范围内的 IC50。Mre11 抑制剂 Mirin 大大降低了 AVP 对 SV40 的 IC50，表明 Mre11 像以前针对 HPV 所显示的那样，保护 PyV 基因组免受 AVP 的作用。这些实验共同表明，AVP 是 PyV 的有效抗病毒药物，其作用机制与 HPV 相似。这些结果表明，AVP 是控制和研究 PyV 生物学的有用工具。这些药物对 BKPyV 和其他 PyV 病原体的潜在用途也具有临床意义。
