一种流感A病毒可以通过改变聚合酶二分化来进化使用人类ANP32E
Carol M Sheppard1, Daniel H Goldhill2,3, Olivia C Swann2
1Department of Infectious Disease, Imperial College London, London, UK. carol.sheppard08@imperial.ac.uk.
Nature communications
|October 10, 2023
概括
流感A病毒通过获得聚合酶突变而进化使用ANP32E,一种新型宿主因子. 这种适应增强了小鼠中的病毒复制,并增加了病毒性.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 宿主-病原体相互作用
背景情况:
- 人类ANP32A和ANP32B是流感病毒复制的关键宿主因素.
- 流感病毒通常无法在缺乏ANP32A和ANP32B的细胞中复制.
研究的目的:
- 在没有正规宿主因素的情况下,研究流感病毒适应机制.
- 通过使用替代宿主蛋白来识别使复制成为可能的病毒突变.
主要方法:
- 在人体ANP32A/ANP32B缺乏细胞中,A型流感病毒的实验进化.
- 对病毒聚合酶突变的分析,使得宿主因子发生变化.
- 在小鼠模型中评估病毒毒性和宿主因子相互作用.
主要成果:
- 流感病毒在编辑的人类细胞中迅速演变为强大的生长.
- 两个聚合酶突变使ANP32E的使用成为可能,这是以前无法使用的宿主因子.
- 这些突变减少了聚合酶二分化,并增强了小鼠ANP32蛋白的利用.
- 进化的病毒在小鼠中表现出增加的毒性.
结论:
- 流感病毒聚合酶可以适应使用替代宿主ANP32家族成员.
- 聚合酶二聚体接口中的突变是宿主因子适应的关键.
- 聚合酶二聚合物对称性和宿主相互作用之间的平衡控制着病毒适应.
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