麻疹病毒核蛋白对线粒体进行向,调节人类呼吸道上皮质中的病毒传播
Lorellin A Durnell-Bettis1, Stephanie E Clark1, Camilla E Hippee1
1Department of Microbiology and Immunology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.
PLoS pathogens
|November 20, 2025
概括
麻疹病毒 (MeV) 使用其核蛋白 (N) 向线粒体,破坏细胞功能和复制,而不会触发典型的免疫反应. 这种新的机制有助于呼吸道细胞中MeV感染.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 麻疹病毒 (MeV) 是高度传染性的,但其在人类呼吸道上皮的感染机制尚不清楚.
- 梅维病毒感染扰乱了线粒体基因表达和呼吸道上皮细胞的功能.
研究的目的:
- 研究MeV如何在人类呼吸道上皮细胞中感染.
- 阐明线粒体在MeV复制和宿主反应中的作用.
主要方法:
- 人类呼吸道原发性上皮细胞 (HAE) 感染MeV.
- 分析线粒体功能,包括膜潜力和超氧化物产生.
- 不同离心法来评估病毒蛋白和基因组定位.
- MeV核蛋白 (N) 的位点导向突变发生,以识别线粒体局部化信号 (MLS).
主要成果:
- MeV复制破坏了线粒体膜潜力并诱导了超氧化物产生,导致cGAS依赖的干扰素刺激基因 (ISG) 表达,而无需干扰素诱导.
- MeV蛋白和基因组被丰富在线粒体的部分.
- 在N蛋白的氨基末端臂 (残留6和13) 中发现了一种新的MLS,这对于线粒体向至关重要.
- 变异MLS的突变MeV显示出改变了HAE中的复制动力学和感染中心形成.
结论:
- MeV N蛋白质含有MLS,该MLS的目标是复制工厂到线粒体,可能逃避正规的RNA感知途径.
- 这种线粒体关联促进了MeV的复制,并调节了宿主反应,为病毒与宿主相互作用提供了新的见解.
- 已识别的MLS是Morbillivirus N蛋白质的独特特征,使它们在Paramyxoviridae家族中区分开来.
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