Spatial and functional arrangement of Ebola virus polymerase inside phase-separated viral factories.

Spatial and functional arrangement of Ebola virus polymerase inside phase-separated viral factories.
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DOI:
10.1038/s41467-023-39821-7
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发表时间:
2023-07-13
影响因子:
16.6
通讯作者:
Saphire, Erica Ollmann
Saphire, Erica Ollmann
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Fang, Jingru;Castillon, Guillaume;Phan, Sebastien;McArdle, Sara;Hariharan, Chitra;Adams, Aiyana;Ellisman, Mark H.;Deniz, Ashok A.;Saphire, Erica Ollmann

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埃博拉病毒(EBOV)感染诱导形成无膜的细胞质室,称为病毒工厂,其中多种病毒蛋白聚集并协调病毒转录、复制和组装。病毒工厂功能的关键是EBOV聚合酶的募集,这是一种介导病毒RNA基因组转录和复制的多功能机器。我们发现细胞内重组的EBOV病毒工厂是生物分子凝聚体,具有依赖于成分的内部交换动力学,可能促进病毒复制。在病毒工厂中,我们发现EBOV聚合酶聚集成疫源地。当启用病毒复制时,这些病灶之间的距离会增加。除了典型的滴状病毒工厂外,我们还报道了EBOV感染期间形成的网络状病毒工厂。与滴状病毒工厂不同,网状工厂对埃博拉病毒的核衣壳组装不起作用。EBOV传播的这种独特观点表明,一种形式-功能关系描述了生物分子凝聚物的物理性质和内部结构如何影响病毒的生物发生。在这里,作者描述了埃博拉病毒诱导的细胞内病毒工厂的相分离特性和内部结构,并将这些特性与病毒生物发生的重要步骤联系起来。
Ebola virus (EBOV) infection induces the formation of membrane-less, cytoplasmic compartments termed viral factories, in which multiple viral proteins gather and coordinate viral transcription, replication, and assembly. Key to viral factory function is the recruitment of EBOV polymerase, a multifunctional machine that mediates transcription and replication of the viral RNA genome. We show that intracellularly reconstituted EBOV viral factories are biomolecular condensates, with composition-dependent internal exchange dynamics that likely facilitates viral replication. Within the viral factory, we found the EBOV polymerase clusters into foci. The distance between these foci increases when viral replication is enabled. In addition to the typical droplet-like viral factories, we report the formation of network-like viral factories during EBOV infection. Unlike droplet-like viral factories, network-like factories are inactive for EBOV nucleocapsid assembly. This unique view of EBOV propagation suggests a form-to-function relationship that describes how physical properties and internal structures of biomolecular condensates influence viral biogenesis. Here, the authors characterized the phase separation properties and internal structures of intracellular viral factories induced by Ebola virus and correlated these properties to important steps of viral biogenesis.
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