在reovirus σ1附着蛋白中的序列多态度调节了小鼠的封装效率和复制
Olivia L Welsh1,2, Alexa N Roth1,2, Danica M Sutherland1,2
1Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Journal of virology
|May 21, 2024
概括
在后代病毒中含量较高的reovirus σ1附着蛋白增加了小鼠的细胞结合和病毒传播. 这种附着蛋白封装效率会影响细胞培养和动物模型中的病毒复制.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 病毒附着蛋白对于宿主细胞相互作用和病毒复制至关重要.
- 病毒附着蛋白封装效率的生物学意义在很大程度上仍未被探索.
- 哺乳动物orthoreovirus (reovirus) σ1蛋白对于附着是必不可少的,其封装效率在各个菌株之间有所不同.
研究的目的:
- 调查 σ1 附着蛋白封装效率在病毒复制中的作用.
- 为了设计具有不同σ1封装效率的reovirus突变.
- 评估 σ1 封装对病毒结合,复制和传播 in vitro 和 in vivo 的影响.
主要方法:
- 改造的reovirus σ1突变病毒,其残留物22和249的替代物.
- 在后代病毒中评估 σ1 封装效率.
- 量化病毒与细胞的结合.
- 测量细胞培养中的病毒复制和小鼠中的传播.
主要成果:
- 在σ1残留22和249的替代改变了σ1封装效率.
- 具有较高 σ1 封闭度的复原病毒与细胞结合得更为敏捷.
- 高 σ1 封闭性转基因病毒在细胞培养中表现出增强的复制和在小鼠中更有效的传播.
- 附着蛋白囊的丰富程度会影响病毒复制.
结论:
- σ1附着蛋白封装效率是重复病毒复制和发病的一个关键因素.
- 增加 σ1 丰富度可以增强病毒结合,细胞进入和传播.
- 这些发现表明,通过操纵s1封装,reovirus有可能作为一种瘤治疗药物.
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