BK polyomavirus (BKPyV) is a ubiquitous pathogen in the human population that is asymptomatic in healthy individuals, but can be life-threatening in those undergoing kidney transplant. To-date, no vaccines or anti-viral therapies are available to treat human BKPyV infections. New therapeutic strategies are urgently required. In this study, using a rational pharmacological screening regimen of known ion channel modulating compounds, we show that BKPyV requires cystic fibrosis transmembrane conductance regulator (CFTR) activity to infect primary renal proximal tubular epithelial cells. Disrupting CFTR function through treatment with the clinically available drug glibenclamide, the CFTR inhibitor CFTR172, or CFTR-silencing, all reduced BKPyV infection. Specifically, time of addition assays and the assessment of the exposure of VP2/VP3 minor capsid proteins indicated a role for CFTR during BKPyV transport to the endoplasmic reticulum, an essential step during the early stages of BKPyV infection. We thus establish CFTR as an important host-factor in the BKPyV life cycle and reveal CFTR modulators as potential anti-BKPyV therapies.

中文翻译：

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格列本脲通过 CFTR 阻断抑制肾细胞中的 BK 多瘤病毒感染。

BK 多瘤病毒 (BKPyV) 是人群中普遍存在的病原体，在健康个体中无症状，但在接受肾移植的患者中可能危及生命。迄今为止，尚无疫苗或抗病毒疗法可用于治疗人类 BKPyV 感染。迫切需要新的治疗策略。在这项研究中，我们使用已知离子通道调节化合物的合理药理学筛选方案，表明 BKPyV 需要囊性纤维化跨膜电导调节剂 (CFTR) 活性来感染原代肾近端肾小管上皮细胞。通过使用临床上可用的药物格列本脲、CFTR 抑制剂 CFTR172 或 CFTR 沉默来破坏 CFTR 功能，都可以减少 BKPyV 感染。具体来说，添加测定的时间和对 VP2/VP3 小衣壳蛋白暴露的评估表明 CFTR 在 BKPyV 转运到内质网期间的作用，这是 BKPyV 感染早期阶段的重要步骤。因此，我们将 CFTR 确立为 BKPyV 生命周期中的重要宿主因素，并揭示 CFTR 调节剂作为潜在的抗 BKPyV 疗法。