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Updated: Apr 12, 2026

Subnanometer-resolution Structural Determination of Hemagglutinin from Cryo-electron Tomography of Influenza Viruses
Published on: November 7, 2025
Influenza virus-mediated membrane fusion: Structural insights from electron microscopy
Juan Fontana1, Alasdair C Steven1
1Laboratory of Structural Biology Research, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Electron microscopy reveals the structural changes in influenza hemagglutinin (HA) during viral entry. This technique visualizes HA-mediated membrane fusion, crucial for understanding flu virus replication and developing antivirals.
Area of Science:
- Structural biology
- Virology
- Cell biology
Background:
- Influenza virus enters host cells via endocytosis.
- Low pH in endosomes triggers hemagglutinin (HA) conformational changes, mediating membrane fusion.
- This fusion releases the viral genome, initiating replication.
Purpose of the Study:
- To investigate the structural basis of hemagglutinin (HA)-mediated membrane fusion.
- To review the contributions of electron microscopy (EM) techniques to understanding influenza virus entry.
Main Methods:
- X-ray crystallography provided pre- and post-fusion HA structures.
- Various EM techniques (cryo-EM, cryo-ET, negative staining, thin section EM) were employed.
- Subtomogram averaging was used to analyze intermediate HA conformations.
Main Results:
- EM visualized influenza virus entry via endocytosis.
- Large-scale HA structural changes upon low pH exposure were observed.
- Acidification-induced changes in M1 matrix layer and viral envelope separation were detected.
- Intermediate HA conformations and virion-liposome fusion were visualized.
Conclusions:
- EM techniques have significantly advanced the characterization of influenza virus-mediated membrane fusion.
- Future EM developments hold potential for further insights into viral entry mechanisms.
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