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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 data-sets of SARS-CoV-2 infected cells for download and smooth online visualization.
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10.1016/j.chom.2020.11.003
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document_parses/pdf_json/4534296f970740e8461f19ec6fe74c28f240f5ef.json
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Integrative imaging reveals SARS-CoV-2 induced reshaping of subcellular morphologies
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