Marburg virus inclusions: A virus-induced microcompartment and interface to multivesicular bodies and the late endosomal compartment
Marburg virus inclusions: A virus-induced microcompartment and interface to multivesicular bodies and the late endosomal compartment
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DOI：
10.1016/j.ejcb.2015.05.006
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发表时间：
2015-07-01
影响因子：
6.6
通讯作者：
Becker, Stephan
中科院分区：
文献类型：
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作者：
Dolnik, Olga;Stevermann, Lea;Becker, Stephan
丝状病毒感染靶细胞会导致病毒诱导的胞浆内含物的形成，其中包含不同成熟阶段的病毒核衣壳。虽然自马尔堡和埃博拉病毒被发现以来，这些包涵体的作用一直不清楚，但最近发现，这些包涵体是病毒复制、核衣壳形成和成熟的场所。活细胞成像分析表明，成熟的核衣壳从包裹体运输到丝状伪足，丝状伪足是主要的萌发部位。此外，包涵体会招募细胞蛋白，这些蛋白已被证明支持核衣壳的运输。例如，肿瘤易感基因101蛋白(Tsg101)与核衣壳蛋白NP中的晚期结构域基序相互作用，并招募肌动蛋白核因子IQGAP1。然后，核衣壳与Tsg101和IQGAP1的复合体沿着肌动蛋白细丝共同运输。我们检测到运输所需的内体分选复合体(ESCRT)的额外蛋白质(Alix、Nedd4和AAA型ATPase Vps4)被招募到包裹体中。总之，这些结果表明，核衣壳招募了促进质膜上病毒萌发的机制。此外，我们确定LAMP1是包裹体中晚期内体间隔的标记，而ER、高尔基体、TGN和早期内体标记缺失。此外，我们还观察到自噬体膜的标志物Lc3存在于包涵体中。包涵体的3D结构显示出一种复杂的结构，似乎适应了细胞和病毒成分之间的密切合作，目的是支持病毒的运输和萌发。(C)2015年爱思唯尔股份有限公司。版权所有。
Filovirus infection of target cells leads to the formation of virally induced cytoplasmic inclusions that contain viral nucleocapsids at different stages of maturation. While the role of the inclusions has been unclear since the identification of Marburg and Ebola viruses, it recently became clear that the inclusions are the sites of viral replication, nucleocapsid formation and maturation. Live cell imaging analyses revealed that mature nucleocapsids are transported from inclusions to the filopodia, which represent the major budding sites. Moreover, inclusions recruit cellular proteins that have been shown to support the transport of nucleocapsids. For example, the tumor susceptibility gene 101 protein (Tsg101) interacts with a late domain motif in the nucleocapsid protein NP and recruits the actin-nucleation factor IQGAP1. Complexes of nucleocapsids together with Tsg101 and IQGAP1 are then co-transported along actin filaments. We detected additional proteins (Alix, Nedd4 and the AAA-type ATPase VPS4) of the endosomal sorting complex required for transport (ESCRT) that are recruited into inclusions. Together, the results suggest that nucleocapsids recruit the machinery that enhances viral budding at the plasma membrane. Furthermore, we identified Lamp1 as a marker of the late endosomal compartment in inclusions, while ER, Golgi, TGN and early endosomal markers were absent. In addition, we observed that LC3, a marker of autophagosomal membranes, was present in inclusions. The 3D structures of inclusions show an intricate structure that seems to accommodate an intimate cooperation between cellular and viral components with the intention to support viral transport and budding. (C) 2015 Elsevier GmbH. All rights reserved.