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Updated: Sep 6, 2025
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Advancing High-Resolution Imaging of Virus Assemblies in Liquid and Ice
Published on: July 20, 2022
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Chikungunya virus assembly and budding visualized in situ using cryogenic electron tomography
David Chmielewski1, Michael F Schmid2, Graham Simmons3,4
1Graduate Program in Biophysics, Stanford University, Stanford, CA, USA.
Nature Microbiology
|June 30, 2022
Summary
Chikungunya virus (CHIKV) assembly involves nucleocapsid scaffolds triggering spike lattice formation. This process transforms cores during budding and offers targets for broad antiviral therapies.
Area of Science:
- Virology
- Structural Biology
- Cell Biology
Background:
- Chikungunya virus (CHIKV) causes arthritogenic disease.
- Alphavirus particle assembly involves a glycoprotein shell and nucleocapsid core.
- The assembly and budding mechanisms of enveloped viruses remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms of CHIKV assembly and budding.
- To investigate the role of nucleocapsid and spike proteins in virus formation.
- To understand antibody-mediated inhibition of alphavirus budding.
Main Methods:
- Cryo-electron tomography (cryo-ET) to visualize CHIKV assembly intermediates in infected cells.
- Subvolume classification and subtomogram averaging to determine structural details.
- Analysis of cells treated with budding-inhibiting antibodies.
Main Results:
- Identified 12 distinct assembly intermediates at the plasma membrane.
- Immature nucleocapsids act as scaffolds for icosahedral spike lattice assembly.
- Spike lattice formation induces transformation of nucleocapsids into icosahedral cores during budding.
- Antibody-induced wider spike spacing inhibits plasma membrane bending and blocks budding.
Conclusions:
- Detailed molecular mechanisms of alphavirus assembly and budding revealed.
- Nucleocapsid-spike interactions are critical for icosahedral particle formation.
- Antibody-mediated inhibition targets spike lattice formation and membrane bending.
- Findings offer insights for developing therapeutics against icosahedral enveloped viruses.
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