美国拉霍亚免疫学研究所Erica Ollmann Saphire团队通过原位冷冻电镜断层扫描，揭示了细胞内埃博拉病毒核衣壳的组装过程。2024年9月17日，《细胞》杂志在线发表了这项成果。

研究人员采用了冷冻电镜断层扫描技术，对转染了病毒蛋白并感染了模型埃博拉病毒的细胞进行研究，以揭示组装中间体，并获得了完整的细胞内组装的9Å分辨率图谱。该结构揭示了一个先前未解决的第三层外层核蛋白（NP）与VP35复合体。

内源性无序区域及其外层NP的C端结构，提供了细胞内核衣壳束之间的恒定宽度，并可能作为病毒基质蛋白的柔性连接物。将细胞内核衣壳与之前在病毒体内的核衣壳结构进行比较发现，核衣壳在病毒体内进一步垂直凝聚。负责核衣壳组装的界面高度保守，为广谱抗病毒药物提供了靶点。

据悉，丝状病毒，包括埃博拉和马尔堡病毒，引发的出血热具有高达90%的致死率。病毒核衣壳通过NP沿病毒基因组聚合，以及病毒蛋白VP24和VP35共同组装。

附：英文原文

Title: Intracellular Ebola virus nucleocapsid assembly revealed by in situ cryo-electron tomography

Author: Reika Watanabe, Dawid Zyla, Diptiben Parekh, Connor Hong, Ying Jones, Sharon L. Schendel, William Wan, Guillaume Castillon, Erica Ollmann Saphire

Issue&Volume: 2024-09-17

Abstract: Filoviruses, including the Ebola and Marburg viruses, cause hemorrhagic fevers with up to 90% lethality. The viral nucleocapsid is assembled by polymerization of the nucleoprotein (NP) along the viral genome, together with the viral proteins VP24 and VP35. We employed cryo-electron tomography of cells transfected with viral proteins and infected with model Ebola virus to illuminate assembly intermediates, as well as a 9 map of the complete intracellular assembly. This structure reveals a previously unresolved third and outer layer of NP complexed with VP35. The intrinsically disordered region, together with the C-terminal domain of this outer layer of NP, provides the constant width between intracellular nucleocapsid bundles and likely functions as a flexible tether to the viral matrix protein in the virion. A comparison of intracellular nucleocapsids with prior in-virion nucleocapsid structures reveals that the nucleocapsid further condenses vertically in the virion. The interfaces responsible for nucleocapsid assembly are highly conserved and offer targets for broadly effective antivirals.

DOI: 10.1016/j.cell.2024.08.044

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00973-5