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Updated: Jun 19, 2026

Method for Measurement of Viral Fusion Kinetics at the Single Particle Level
Published on: September 7, 2009
Molecular mechanisms of flavivirus membrane fusion
Karin Stiasny1, Richard Fritz, Karen Pangerl
1Institute of Virology, Medical University of Vienna, AT, Austria. karin.stiasny@meduniwien.ac.at
Abstract:
Flaviviruses comprise a number of important human pathogens including yellow fever, dengue, West Nile, Japanese encephalitis and tick-borne encephalitis viruses. They are small enveloped viruses that enter cells by receptor-mediated endocytosis and release their nucleocapsid into the cytoplasm by fusing their membrane with the endosomal membrane. The fusion event is triggered by the acidic pH in the endosome and is mediated by the major envelope protein E. Based on the atomic structures of the pre- and post-fusion conformations of E, a fusion model has been proposed that includes several steps leading from the metastable assembly of E at the virion surface to membrane merger and fusion pore formation trough conversion of E into a stable trimeric post-fusion conformation. Using recombinant subviral particles of tick-borne encephalitis virus as a model, we have defined individual steps of the molecular processes underlying the flavivirus fusion mechanisms. This includes the identification of a conserved histidine as being part of the pH sensor in the fusion protein that responds to the acidic pH and thus initiates the structural transitions driving fusion.
Insights
Flaviviruses like dengue use their envelope protein E to fuse with host cells. A conserved histidine in the fusion protein acts as a pH sensor, initiating fusion at acidic endosomal pH.
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- Flaviviruses are significant human pathogens, including dengue and West Nile virus.
- Viral entry involves receptor-mediated endocytosis and fusion of viral and endosomal membranes, mediated by the envelope protein E.
- The fusion process is triggered by acidic pH within the endosome.
Purpose of the Study:
- To elucidate the molecular mechanisms of flavivirus-host membrane fusion.
- To define individual steps in the flavivirus fusion process using tick-borne encephalitis virus as a model.
Main Methods:
- Utilized recombinant subviral particles of tick-borne encephalitis virus.
- Analyzed structural transitions of the envelope protein E.
- Identified key residues involved in pH sensing and fusion initiation.
Main Results:
- Defined individual steps in the flavivirus membrane fusion mechanism.
- Identified a conserved histidine residue crucial for pH sensing.
- Demonstrated that this histidine initiates structural transitions in protein E upon exposure to acidic pH.
Conclusions:
- The conserved histidine acts as a critical pH sensor in the flavivirus fusion protein E.
- This pH sensing initiates the structural cascade leading to viral-endosomal membrane fusion.
- Provides a detailed molecular model for flavivirus entry and fusion.
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