The Structure of an Infectious Human Polyomavirus and Its Interactions with Cellular Receptors.
The Structure of an Infectious Human Polyomavirus and Its Interactions with Cellular Receptors.
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DOI：
10.1016/j.str.2018.03.019
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发表时间：
2018-06-05
期刊：
影响因子：
--
通讯作者：
Ranson NA
中科院分区：
文献类型：
--
作者：
Hurdiss DL;Frank M;Snowden JS;Macdonald A;Ranson NA
BK多瘤病毒（BKV）在免疫抑制患者中引起多瘤病毒相关肾病和出血性膀胱炎。这些是我们目前治疗选择有限的疾病，但潜在的治疗方法可能包括移植前接种多价BKV疫苗或抑制衣壳组装或阻断附着和进入靶细胞的治疗剂。在这种努力中，一个有用的工具将是感染性BKV病毒粒子的高分辨率结构，以及它如何与其全部细胞受体库相互作用。我们提出了3.4-croyotelectron显微镜结构的本地，感染性BKV的复杂的受体片段GT 1b神经节苷脂。我们还提出了结构证据表明，BKV可以利用糖胺聚糖作为附着受体。这项工作突出了支持衣壳稳定性的特征，并为合理设计和开发BKV相关疾病急需的药理学干预提供了平台。在3.4 μ m分辨率下展示天然感染性BKV病毒粒子的冷冻电镜结构揭示介导衣壳组装的五聚体间相互作用确定BKV与GT 1b神经节苷脂受体片段的相互作用确定病毒粒子表面糖胺聚糖结合的可能位点BK多瘤病毒在免疫抑制中引起几种衰弱性疾病，目前尚无有效的治疗方法。Hurdiss等人呈现BK的高分辨率结构和与不同细胞受体的复合物。这项工作为合理设计和开发BK相关疾病急需的靶向药物干预提供了平台。
BK polyomavirus (BKV) causes polyomavirus-associated nephropathy and hemorrhagic cystitis in immunosuppressed patients. These are diseases for which we currently have limited treatment options, but potential therapies could include pre-transplant vaccination with a multivalent BKV vaccine or therapeutics which inhibit capsid assembly or block attachment and entry into target cells. A useful tool in such efforts would be a high-resolution structure of the infectious BKV virion and how this interacts with its full repertoire of cellular receptors. We present the 3.4-Å cryoelectron microscopy structure of native, infectious BKV in complex with the receptor fragment of GT1b ganglioside. We also present structural evidence that BKV can utilize glycosaminoglycans as attachment receptors. This work highlights features that underpin capsid stability and provides a platform for rational design and development of urgently needed pharmacological interventions for BKV-associated diseases. Present the cryo-EM structure of native, infectious BKV virion at 3.4 Å resolution Reveal interpentamer interactions that mediate capsid assembly Determine the interaction of BKV with a receptor fragment of GT1b ganglioside Identify possible sites for glycosaminoglycan binding on the virion surface BK polyomavirus causes several debilitating diseases in the immunosuppressed with no effective treatments currently available. Hurdiss et al. present the high-resolution structure of BK and complexes with distinct cellular receptors. This work provides a platform for rational design and development of urgently needed targeted pharmacological interventions for BK-associated diseases.
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