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Integrative Imaging Reveals SARS-CoV-2-Induced Reshaping of Subcellular Morphologies.
Mirko Cortese1, Ji-Young Lee2, Berati Cerikan1
1Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
SARS-CoV-2 infection disrupts cell organelles, including the Golgi and mitochondria, and alters the cytoskeleton. Inhibiting cytoskeleton dynamics reduces viral replication, offering new therapeutic insights.
Area of Science:
- Cell Biology
- Virology
- Microscopy
Background:
- SARS-CoV-2 pathogenesis involves inflammation and cell damage.
- Understanding virus-induced organelle changes is crucial for treatment development.
Purpose of the Study:
- To investigate morphological organelle alterations in SARS-CoV-2-infected human lung epithelial cells.
- To elucidate the role of cytoskeleton remodeling in viral replication.
Main Methods:
- Integrative imaging analysis using 3D electron microscopy.
- Live cell imaging with an infection sensor.
- Pharmacological inhibition of cytoskeleton dynamics.
Main Results:
- Observed extensive Golgi fragmentation, mitochondrial network alterations, and peroxisome recruitment to viral replication sites (DMVs).
- Identified endoplasmic reticulum tethering of DMVs, offering insights into viral replication coordination.
- Demonstrated profound cytoskeleton remodeling and suppression of SARS-CoV-2 replication upon pharmacological inhibition.
Conclusions:
- SARS-CoV-2 infection induces significant cytopathic effects through organelle perturbation and cytoskeleton remodeling.
- Targeting cytoskeleton dynamics presents a potential therapeutic strategy against SARS-CoV-2.
- Provided a public repository of 3D datasets for further research on SARS-CoV-2-infected cells.
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