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超分辨率显微镜和深度学习鉴定寨卡病毒内质网的重排。

Super resolution microscopy and deep learning identify Zika virus reorganization of the endoplasmic reticulum.

机构信息

Life Sciences Institute, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.

Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.

出版信息

Sci Rep. 2020 Dec 1;10(1):20937. doi: 10.1038/s41598-020-77170-3.

DOI:10.1038/s41598-020-77170-3
PMID:33262363
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7708840/
Abstract

The endoplasmic reticulum (ER) is a complex subcellular organelle composed of diverse structures such as tubules, sheets and tubular matrices. Flaviviruses such as Zika virus (ZIKV) induce reorganization of ER membranes to facilitate viral replication. Here, using 3D super resolution microscopy, ZIKV infection is shown to induce the formation of dense tubular matrices associated with viral replication in the central ER. Viral non-structural proteins NS4B and NS2B associate with replication complexes within the ZIKV-induced tubular matrix and exhibit distinct ER distributions outside this central ER region. Deep neural networks trained to distinguish ZIKV-infected versus mock-infected cells successfully identified ZIKV-induced central ER tubular matrices as a determinant of viral infection. Super resolution microscopy and deep learning are therefore able to identify and localize morphological features of the ER and allow for better understanding of how ER morphology changes due to viral infection.

摘要

内质网(ER)是一种复杂的亚细胞细胞器,由各种结构组成,如小管、薄片和管状基质。寨卡病毒(ZIKV)等黄病毒诱导内质网膜的重排,以促进病毒复制。在这里,使用 3D 超分辨率显微镜,显示寨卡病毒感染诱导致密管状基质的形成,该基质与中央内质网中的病毒复制相关。病毒非结构蛋白 NS4B 和 NS2B 与寨卡病毒诱导的管状基质内的复制复合物结合,并在该中央内质网区域之外表现出不同的内质网分布。经过训练以区分寨卡病毒感染细胞与模拟感染细胞的深度神经网络成功地将寨卡病毒诱导的中央内质网管状基质识别为病毒感染的决定因素。超分辨率显微镜和深度学习因此能够识别和定位内质网的形态特征,并更好地了解内质网形态如何因病毒感染而发生变化。

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本文引用的文献

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Zika NS2B is a crucial factor recruiting NS3 to the ER and activating its protease activity.寨卡 NS2B 是一个关键因素,招募 NS3 到内质网并激活其蛋白酶活性。
Virus Res. 2020 Jan 2;275:197793. doi: 10.1016/j.virusres.2019.197793. Epub 2019 Oct 29.
2
ER-shaping atlastin proteins act as central hubs to promote flavivirus replication and virion assembly.卷曲螺旋蛋白在 ER 中作为中心枢纽促进黄病毒的复制和病毒粒子的组装。
Nat Microbiol. 2019 Dec;4(12):2416-2429. doi: 10.1038/s41564-019-0586-3. Epub 2019 Oct 21.
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Atlastin Endoplasmic Reticulum-Shaping Proteins Facilitate Zika Virus Replication.
病毒对细胞器膜接触位点的调控。
PLoS Biol. 2024 Mar 5;22(3):e3002529. doi: 10.1371/journal.pbio.3002529. eCollection 2024 Mar.
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Membrane contact site detection (MCS-DETECT) reveals dual control of rough mitochondria-ER contacts.膜接触位点检测(MCS-DETECT)揭示了粗糙内质网-线粒体接触的双重控制。
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