适应在人类细胞中复制的小鼠诺罗病毒突变揭示了进入后的限制
Melissa R Budicini1, Valerie J Rodriguez-Irizarry1, Robert W Maples1
1Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Journal of virology
|April 23, 2024
概括
适应人类细胞的小鼠诺罗病毒 (MNV) 显示出增加的复制,但在小鼠中降低了健康状况. 这表明,在非本地宿主中增强的病毒复制损害了自然宿主环境中的功能时,存在一种权衡.
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:
- 像小鼠诺病毒 (MNV) 这样的RNA病毒由于易发生错误的RNA聚合酶而表现出遗传多样性.
- 病毒热带和宿主范围受到宿主因素的影响,包括病毒受体和细胞内复制机制.
研究的目的:
- 通过将病毒适应到人类细胞中来研究控制MNV热带和宿主限制的因素.
- 识别赋予非小鼠细胞增强复制的突变,并了解它们对病毒适应性的影响.
主要方法:
- 在HeLa (人类) 细胞中传递MNV以选择适应变异.
- 基因组分析以确定适应病毒中的突变.
- 评估人类和小鼠细胞中的病毒复制和附着,具有和没有受体表达.
- 评估小鼠细胞和小鼠中的病毒适应性.
主要成果:
- 在人类细胞中传递的MNV获得了突变,主要是在非结构编码区域,增强复制.
- 调整后的MNV在人体细胞中增加了后入细胞复制,表明后入细胞阻断.
- 在NS1蛋白中的三种突变足以增强人类细胞复制.
- 适应人类细胞的MNV在小鼠细胞和小鼠中表现出降低的适应性,表明适应性权衡.
结论:
- MNV 热带性是由受体可用性和入境后宿主因素决定的.
- 适应非本地宿主可能会导致自然宿主的适应性降低,突出演化权衡.
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