阳性选择分析确定了单个WWE域残留物,该残留物将ZAP塑造为一种更强大的对α病毒的限制因子
Serina Huang1, Juliana Girdner2,3, LeAnn P Nguyen3,4
1Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
PLoS pathogens
|August 29, 2024
概括
宿主限制因素如指抗病毒蛋白 (ZAP) 进化以对抗病毒. 研究人员确定了ZAP关键突变,通过改善病毒转化抑制来增强其对α病毒的抗病毒活性.
科学领域:
- 进化生物学是进化的生物学.
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- 宿主限制因素,如指抗病毒蛋白 (ZAP),由干扰素途径上调,以对抗病毒感染.
- 这些因素的演变是由宿主病毒冲突驱动的,导致相互作用蛋白质的快速适应.
- 了解ZAP的进化适应可以阐明其抗病毒机制和域功能.
研究的目的:
- 通过强大的进化分析,在哺乳动物ZAP中确定积极选择的位点.
- 调查这些选定的部位对ZAP对alphavirus的抗病毒活性的影响.
- 探索ADP-ribosylation在天生的免疫和病毒对抗策略中的作用.
主要方法:
- 通过使用先进的计算方法对261只哺乳动物ZAP Ortholog进行了积极选择分析.
- 生成ZAP诱导细胞系,在积极选择的残留物中发生突变.
- 评估了ZAP突变对阿尔法病毒复制和ZAP相关活动的影响,包括聚ADP-ribose (PAR) 结合.
主要成果:
- 在哺乳动物ZAP的所有领域中确定了七个积极选择的地点.
- 第二个WWE域 (N658A) 的突变显著增强了ZAP抑制阿尔法病毒复制的能力,特别是Sindbis病毒.
- 该N658A突变显示了减少的PAR结合,这表明PAR结合和抗病毒功效之间的复杂相互作用.
结论:
- 扎普的第二个WWE域名对于增强其抗病毒功效至关重要.
- 调节PAR结合影响ZAP的抗病毒活性,提供了对宿主病毒共同进化的见解.
- 这项研究揭示了ADP-ribosylation在先天免疫和病毒逃避策略中的作用.
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