Review Article

Amino Acids

, Volume 41, Issue 5, pp 1159-1163

Molecular mechanisms of flavivirus membrane fusion

  • Karin StiasnyAffiliated withInstitute of Virology, Medical University of Vienna Email author 
  • , Richard FritzAffiliated withInstitute of Virology, Medical University of Vienna
  • , Karen PangerlAffiliated withInstitute of Virology, Medical University of Vienna
  • , Franz X. HeinzAffiliated withInstitute of Virology, Medical University of Vienna

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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.


Flavivirus Membrane fusion Viral fusion protein Fusion trigger Histidine