流感A病毒颠覆LC3-pericentrin dynein适应器复合体,使其进入宿主细胞质
Yingying Cong1,2,3, Pauline Verlhac3, Benjamin B Green4
1Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Science advances
|June 11, 2025
概括
流感A病毒使用轻链3蛋白 (LC3s) 和周心素 (PCNT) 结合dynein电机进行病毒脱涂. 这种机制与攻击性处理机器相结合,便于病毒进入和感染.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 流感A病毒 (IAV) 感染始于内细胞结合和病毒颗粒 (VP) 融合在内基因组内.
- 病毒核糖蛋白 (vRNP) 随后释放到细胞质中,称为脱涂,对于IAV复制至关重要,但尚未完全阐明.
- 在这个过程中,攻击性处理机器 (APM) 起到辅助作用.
研究的目的:
- 为了阐明流感A病毒在内分泌体上脱皮的机制.
- 为了确定参与vRNP释放和细胞质进入的宿主因素.
- 为了研究LC3蛋白,周心素和IAV感染中的APM之间的相互作用.
主要方法:
- 使用基因沉默技术减少轻链3蛋白 (LC3s) 和周心蛋白 (PCNT).
- 在蛋白质耗尽后评估IAV细胞质进入和感染效率.
- 对vRNP与dynein 1电机结合的分析.
- 调查静止基因组脱乙酶6 (HDAC6) 与LC3或PCNT耗尽结合的效果.
主要成果:
- LC3s和PCNT形成了一个适配器复合体,对于将vRNP与dynein 1电机结合至关重要.
- 这种LC3-PCNT复合体有助于IAV在内体上脱涂,独立于自或中心体组装作用.
- LC3s或PCNT的枯竭显著抑制IAV进入细胞质和随后的感染.
- 结合LC3s或PCNT与HDAC6的沉默,进一步减少IAV感染,表明冗余机制.
结论:
- IAV使用了一种涉及LC3s和PCNT的新途径来启动dynein电机,以有效地脱涂.
- 这种LC3-PCNT-dynein轴代表了这些蛋白质在病毒复制中的关键,非自相关的功能.
- IAV使用至少两种冗余策略,涉及APM和LC3-PCNT复合体,以劫持用于病毒脱涂和感染的dynein电机.
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