Electron tomography of viruses
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Updated: Jul 10, 2026

Scanning Transmission Electron Microscopy Tomography in Virology: 3D Imaging of High-pressure Frozen, Freeze-substituted Samples
Published on: August 6, 2025
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>
Abstract:
Understanding the molecular architectures of enveloped and complex viruses is a challenging frontier in structural biology. In these viruses, the structural and compositional variation from one viral particle to another generally precludes the use of either crystallization or image averaging procedures that have been successfully implemented in the past for highly symmetric viruses. While advances in cryo electron tomography of unstained specimens provide new opportunities for identification and molecular averaging of individual subcomponents such as the surface glycoprotein spikes on purified viruses, electron tomography of stained and plunge-frozen cells is being used to visualize the cellular context of viral entry and replication. Here, we review recent developments in both areas as they relate to our understanding of the biology of heterogeneous and pleiomorphic viruses.
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