艾滋病毒-1通过第二位突变适应失去的IP6协调,恢复状状体组件
Alex Kleinpeter1, Donna L Mallery2, Nadine Renner2
1Virus-Cell Interaction Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702-1201, USA. alex.kleinpeter@nih.gov.
Nature communications
|September 13, 2024
概括
艾滋病毒-1囊蛋白中的突变显示,Lys-25对于病毒复制或组装并不重要. 补偿突变通过重新建立体体形成和适当组装来恢复功能.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 人类免疫缺陷病毒1型 (HIV-1) 囊是病毒复制必不可少的蛋白质外.
- 体蛋白 (CA) 形成六合体和五合体 (体),其中有一个中央孔隙,假设调节组装和核酸进口.
- 由CA残留物Arg-18 (R18) 和Lys-25 (K25) 形成的带正电荷的环被认为是介导这些孔隙功能.
研究的目的:
- 通过强迫进化研究R18和K25在HIV-1囊功能和复制中的作用.
- 为了确定补偿突变,在K25残留物中发生突变后恢复病毒适应性.
主要方法:
- 强制进化HIV-1病毒的R18和K25突变.
- 对病毒复制适应性,逆转录和感染的分析.
- 在体外和体外囊组装测试.
- 绘制第二位抑制器突变的映射.
主要成果:
- R18突变体表现出完全无法复制.
- K25A突变者获得了补偿突变,恢复了接近野生类型的复制能力.
- 这些抑制剂可以挽救逆转录和感染,而不会重新引入丢失的孔电荷.
- 补偿突变恢复了体形成,并使闭合的形体组装 in vitro 和 in virions 成为可能.
结论:
- 对于HIV-1核酸进口或囊组装,Lys-25 (K25) 本质上并不需要.
- 艾滋病毒-1需要一个精确的六合体:五合体平衡,以便适当的囊组装.
- 补偿突变可以通过调整孔突变后的这种平衡来恢复病毒健康.
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