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

Amino Acids
|November 3, 2009
PubMed

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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