Integrative Imaging Reveals SARS-CoV-2-Induced Reshaping of Subcellular Morphologies.
FIB-SEM
Golgi
coronavirus
cytoskeleton
electron tomography
intermediate filaments
live cell imaging
membrane remodeling
peroxisomes
viral replication organelles
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
09 12 2020
09 12 2020
Historique:
received:
05
08
2020
revised:
30
09
2020
accepted:
12
11
2020
pubmed:
28
11
2020
medline:
29
12
2020
entrez:
27
11
2020
Statut:
ppublish
Résumé
Pathogenesis induced by SARS-CoV-2 is thought to result from both an inflammation-dominated cytokine response and virus-induced cell perturbation causing cell death. Here, we employ an integrative imaging analysis to determine morphological organelle alterations induced in SARS-CoV-2-infected human lung epithelial cells. We report 3D electron microscopy reconstructions of whole cells and subcellular compartments, revealing extensive fragmentation of the Golgi apparatus, alteration of the mitochondrial network and recruitment of peroxisomes to viral replication organelles formed by clusters of double-membrane vesicles (DMVs). These are tethered to the endoplasmic reticulum, providing insights into DMV biogenesis and spatial coordination of SARS-CoV-2 replication. Live cell imaging combined with an infection sensor reveals profound remodeling of cytoskeleton elements. Pharmacological inhibition of their dynamics suppresses SARS-CoV-2 replication. We thus report insights into virus-induced cytopathic effects and provide alongside a comprehensive publicly available repository of 3D datasets of SARS-CoV-2-infected cells for download and smooth online visualization.
Identifiants
pubmed: 33245857
pii: S1931-3128(20)30620-X
doi: 10.1016/j.chom.2020.11.003
pmc: PMC7670925
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
853-866.e5Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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