Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Virology. 2022 Oct;575:74-82. doi: 10.1016/j.virol.2022.08.015. Epub 2022 Aug 30.
Seneca Valley virus (SVV) is a newly discovered picornavirus in the Senecavirus genus. SVV-001 strain has shown promise as an oncolytic virus against tumors with neuroendocrine features. There is a need to use a structure-based approach to develop virus-like particles capable to mimicking the architecture of naturally occurring empty capsids that can be used as vaccines or as carriers for targeted cancer treatment. However, these empty capsids are inherently less stable, and tedious to purify. This warrants investigation into factors which confer the SVV capsid stability and into combining this knowledge to recombinantly express stable SVV VLPs. In this study, we isolated a thermostable mutant of SVV by thermal selection assays and we characterized a single mutation located in a capsid protein. The cryo-EM map of this mutant showed conformational shifts that facilitated the formation of additional hydrogen bonds and aromatic interactions, which could serve as capsid stabilizing factors.
森戈维亚病毒（SVV）是一种新发现的正呼肠孤病毒属病毒。SVV-001 株已显示出作为一种溶瘤病毒对抗具有神经内分泌特征的肿瘤的潜力。需要使用基于结构的方法来开发能够模拟天然存在的空衣壳结构的病毒样颗粒，这些空衣壳可作为疫苗或作为针对癌症的靶向治疗载体。然而，这些空衣壳本身的稳定性较差，纯化过程繁琐。因此，有必要研究赋予 SVV 衣壳稳定性的因素，并将这些知识结合起来，重组表达稳定的 SVV VLP。在这项研究中，我们通过热选择实验分离出 SVV 的耐热突变体，并对位于衣壳蛋白上的单个突变进行了特征分析。该突变体的 cryo-EM 图谱显示构象发生了变化，从而形成了更多的氢键和芳香族相互作用，这些相互作用可能作为衣壳稳定因素。
