竞技病毒糖蛋白中的源性结构变化与病毒蛋白活性有关
You Zhang1,2, Joanne York3, Melinda A Brindley4
1Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
PLoS pathogens
|July 26, 2023
概括
拉萨病毒 (LASV) 糖蛋白复合体 (GPc) 在融合之前增加病毒膜的透性,这是与形状变化相关的过程. 这种类似于病毒蛋白的活性可能有助于病毒的进入和核糖蛋白的释放.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 包裹病毒利用内体体融合进入细胞.
- 病毒融合通常不会改变病毒膜的透性.
- 拉萨病毒 (LASV) 葡萄糖蛋白复合体 (GPc) 介导的融合之前,病毒膜的透性增加和内部酸化.
研究的目的:
- 为了研究LASV独特的融合表型背后的机制.
- 确定GPc形状变化在病毒膜透中的作用.
- 探索这种活动对病毒感染的影响.
主要方法:
- 单个伪病毒在活细胞中追踪.
- 使用小分子聚变抑制剂和特定突变.
- 采用基于lentivirus的伪病毒和类似arenavirus的粒子.
主要成果:
- LASV GPc经历了融合性形状重组,增加了病毒膜的透性.
- 抑制剂和阻断GPc重新折叠的突变阻止了膜透.
- 增加的透性发生在内体成熟的早期,由细胞接触促进.
- 这种现象在不同的竞技病毒糖蛋白和细胞类型中得到保存.
结论:
- 由于低pH值和细胞因素引发的LASV GPc的形态变化,导致病毒膜透.
- 这种类似于病毒的活性先于并可能增强病毒融合和融合后事件.
- 这些研究结果提供了有关arenavirus入侵机制和潜在治疗点的见解.
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