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Scanning Transmission Electron Microscopy Tomography in Virology: 3D Imaging of High-pressure Frozen, Freeze-substituted Samples
Published on: August 6, 2025
Electron tomography of viruses.
Sriram Subramaniam1, Alberto Bartesaghi, Jun Liu
1Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, United States. ss1@nih.gov <ss1@nih.gov>
Current Opinion in Structural Biology
|October 30, 2007
Summary
Structural biology faces challenges with complex viruses due to particle variation. Recent cryo-electron tomography advances aid in visualizing viral structures and cellular context for heterogeneous viruses.
Area of Science:
- Structural biology
- Virology
- Microscopy
Background:
- Enveloped and complex viruses exhibit significant structural and compositional heterogeneity.
- Traditional methods like crystallization and image averaging are often unsuitable for these viruses.
- Understanding viral architecture is crucial for comprehending viral entry and replication.
Purpose of the Study:
- To review recent advancements in cryo-electron tomography (cryo-ET) for studying heterogeneous and pleiomorphic viruses.
- To highlight how cryo-ET aids in understanding viral molecular architectures and cellular interactions.
- To discuss the application of cryo-ET in both purified viral systems and cellular contexts.
Main Methods:
- Cryo-electron tomography (cryo-ET) of unstained specimens for subcomponent analysis.
- Cryo-ET of stained and plunge-frozen cells for visualizing cellular context.
- Molecular averaging techniques applied to individual subcomponents like glycoprotein spikes.
Main Results:
- Cryo-ET enables identification and averaging of individual subcomponents (e.g., glycoprotein spikes) on purified viruses.
- Cryo-ET of cellular samples visualizes the in situ viral entry and replication processes.
- These methods overcome limitations of traditional techniques for non-uniform viral particles.
Conclusions:
- Recent cryo-ET developments offer powerful tools for dissecting the biology of heterogeneous and pleiomorphic viruses.
- These techniques advance our understanding of viral structure, assembly, and interaction with host cells.
- Cryo-ET is becoming indispensable in structural biology and virology for complex viral systems.
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