Ultrastructural Characterization of Zika Virus Replication Factories.
Ultrastructural Characterization of Zika Virus Replication Factories.
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DOI：
10.1016/j.celrep.2017.02.014
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发表时间：
2017-02-28
期刊：
影响因子：
8.8
通讯作者：
Bartenschlager R
中科院分区：
文献类型：
--
作者：
Cortese M;Goellner S;Acosta EG;Neufeldt CJ;Oleksiuk O;Lampe M;Haselmann U;Funaya C;Schieber N;Ronchi P;Schorb M;Pruunsild P;Schwab Y;Chatel-Chaix L;Ruggieri A;Bartenschlager R
随着寨卡病毒（ZIKV）感染的大流行蔓延，全球出现了一个担忧，该病毒感染可导致成人和新生儿出现严重的神经系统症状。ZIKV是在病毒诱导的膜复制工厂（RF）中复制的正链RNA病毒。在这里，我们使用各种成像技术来研究ZIKV RF的超微结构细节及其与宿主细胞器的关系。对感染ZIKV的人肝细胞和神经祖细胞的分析揭示了内质网（ER）膜内陷，其含有朝向胞质溶胶的孔样开口，这让人联想到登革热病毒感染的细胞中的RF。MR 766非洲菌株和H/PF/2013亚洲菌株（后者与神经系统疾病相关）均诱导具有相似结构的RF。重要的是，ZIKV感染引起微管和中间丝的剧烈重组，形成围绕病毒RF的笼状结构。一致地，ZIKV复制被细胞因子靶向药物抑制。因此，ZIKV RF与宿主细胞细胞骨架的重排紧密连接。ZIKV诱导细胞骨架的深刻改变ZIKV复制工厂周围的微管和中间丝ZIKV复制对靶向细胞因子的药物敏感Cortese et al.显示人肝癌和神经元祖细胞中的ZIKV感染诱导细胞架构的剧烈结构修饰。微管和中间丝围绕着病毒复制工厂，病毒复制工厂由囊泡组成，囊泡对应于ER膜向ER腔的内陷。重要的是，微管柔性的改变损害ZIKV复制。
A global concern has emerged with the pandemic spread of Zika virus (ZIKV) infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs). Here we used various imaging techniques to investigate the ultrastructural details of ZIKV RFs and their relationship with host cell organelles. Analyses of human hepatic cells and neural progenitor cells infected with ZIKV revealed endoplasmic reticulum (ER) membrane invaginations containing pore-like openings toward the cytosol, reminiscent to RFs in Dengue virus-infected cells. Both the MR766 African strain and the H/PF/2013 Asian strain, the latter linked to neurological diseases, induce RFs of similar architecture. Importantly, ZIKV infection causes a drastic reorganization of microtubules and intermediate filaments forming cage-like structures surrounding the viral RF. Consistently, ZIKV replication is suppressed by cytoskeleton-targeting drugs. Thus, ZIKV RFs are tightly linked to rearrangements of the host cell cytoskeleton. ZIKV induces ER membrane invaginations similar to Dengue virus ZIKV induces profound alterations of the cytoskeleton Microtubules and intermediate filaments surround the ZIKV replication factory ZIKV replication is sensitive to cytoskeleton-targeting drugs Cortese et al. show that ZIKV infection in both human hepatoma and neuronal progenitor cells induces drastic structural modification of the cellular architecture. Microtubules and intermediate filaments surround the viral replication factory composed of vesicles corresponding to ER membrane invagination toward the ER lumen. Importantly, alteration of microtubule flexibility impairs ZIKV replication.