Integrative Imaging Reveals SARS-CoV-2 Induced Reshaping of Subcellular Morphologies

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 employed an integrative light and electron microscopy based imaging analysis to determine morphological organelle alterations induced in SARS-CoV-2 infected human lung epithelial cells. We report 3D 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 remodelling of cytoskeleton elements; pharmacological inhibition of their dynamics strongly suppresses SARS-CoV-2 replication. Taken together, we provide critical insights into virus-induced cytopathic effects, while alongside presenting a comprehensive and publicly available repository of 3D data-sets of SARS-CoV-2 infected cells. Funding: This work was supported in part by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project number 240245660 – SFB 1129 (TP11, TP13, TP14 and project Z2) to R.B., A.R., S.B. and Y.S. R.B. was supported in addition by the German Center for Infection Research (DZIF), project numbers 8029801806 and 8029705705, and the DFG, project number 272983813 – TRR 179.SB and MS received additional financial support from the DFG, project number 415089553 (Heisenberg) and 272983813 (TRR179) to S.B. and project number 416072091 to MS. Conflict of Interest: The authors declare no competing interests.