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由VP24调控的埃博拉病毒核衣壳组装及功能的结构基础

Structural basis for Ebola virus nucleocapsid assembly and function regulated by VP24.

作者信息

Fujita-Fujiharu Yoko, Hu Shangfan, Hirabayashi Ai, Takamatsu Yuki, Ng Yen Ni, Houri Kazuya, Muramoto Yukiko, Nakano Masahiro, Sugita Yukihiko, Noda Takeshi

机构信息

Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Laboratory of Ultrastructural Virology, Graduate School of Biostudies, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

出版信息

Nat Commun. 2025 Mar 10;16(1):2171. doi: 10.1038/s41467-025-57236-4.

DOI:10.1038/s41467-025-57236-4
PMID:40064872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11894184/
Abstract

The Ebola virus, a member of the Filoviridae family, causes severe hemorrhagic fever in humans. Filamentous virions contain a helical nucleocapsid responsible for genome transcription, replication, and packaging into progeny virions. The nucleocapsid consists of a helical nucleoprotein (NP)-viral genomic RNA complex forming the core structure, to which VP24 and VP35 bind externally. Two NPs, each paired with a VP24 molecule, constitute a repeating unit. However, the detailed nucleocapsid structure remains unclear. Here, we determine the nucleocapsid-like structure within virus-like particles at 4.6 Å resolution using single-particle cryo-electron microscopy. Mutational analysis identifies specific interactions between the two NPs and two VP24s and demonstrates that each of the two VP24s in different orientations distinctively regulates nucleocapsid assembly, viral RNA synthesis, intracellular transport of the nucleocapsid, and infectious virion production. Our findings highlight the sophisticated mechanisms underlying the assembly and functional regulation of the nucleocapsid and provide insights into antiviral development.

摘要

埃博拉病毒是丝状病毒科的成员，可导致人类严重出血热。丝状病毒粒子包含一个负责基因组转录、复制以及包装进子代病毒粒子的螺旋核衣壳。核衣壳由形成核心结构的螺旋核蛋白（NP）-病毒基因组RNA复合物组成，VP24和VP35在外部与之结合。两个NP与每个VP24分子配对，构成一个重复单元。然而，核衣壳的详细结构仍不清楚。在此，我们使用单颗粒冷冻电子显微镜以4.6埃的分辨率确定了病毒样颗粒内的核衣壳样结构。突变分析确定了两个NP与两个VP24之间的特定相互作用，并表明处于不同方向的两个VP24各自独特地调节核衣壳组装、病毒RNA合成、核衣壳的细胞内运输以及传染性病毒粒子的产生。我们的研究结果突出了核衣壳组装和功能调节背后的复杂机制，并为抗病毒药物研发提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/699f9ae69b02/41467_2025_57236_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/18eeb215ef74/41467_2025_57236_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/58fc052df703/41467_2025_57236_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/881397ac19b2/41467_2025_57236_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/27bb5ff5a719/41467_2025_57236_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/2a0a513b8f62/41467_2025_57236_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/69a348abf189/41467_2025_57236_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/6c9e5a56bb27/41467_2025_57236_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/699f9ae69b02/41467_2025_57236_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/18eeb215ef74/41467_2025_57236_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/58fc052df703/41467_2025_57236_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/881397ac19b2/41467_2025_57236_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/27bb5ff5a719/41467_2025_57236_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/2a0a513b8f62/41467_2025_57236_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/69a348abf189/41467_2025_57236_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/6c9e5a56bb27/41467_2025_57236_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e62f/11894184/699f9ae69b02/41467_2025_57236_Fig8_HTML.jpg

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