Entry Functions and Antigenic Structure of Flavivirus Envelope Proteins

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. Karin Stiasny,
  2. Stefan Kiermayr and
  3. Franz X. Heinz

Published Online: 7 OCT 2008

DOI: 10.1002/0470058005.ch5

New Treatment Strategies for Dengue and Other Flaviviral Diseases: Novartis Foundation Symposium 277

New Treatment Strategies for Dengue and Other Flaviviral Diseases: Novartis Foundation Symposium 277

How to Cite

Stiasny, K., Kiermayr, S. and Heinz, F. X. (2008) Entry Functions and Antigenic Structure of Flavivirus Envelope Proteins, in New Treatment Strategies for Dengue and Other Flaviviral Diseases: Novartis Foundation Symposium 277 (eds G. Bock and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470058005.ch5

Author Information

  1. Institute of Virology, Medical University of Vienna, Kinderspitalgasse 15, A1095 Vienna, Austria

  1. This paper was presented at the symposium by Franz Heinz, to whom all correspondence should be addressed

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 25 AUG 2006

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470016435

Online ISBN: 9780470058008

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Keywords:

  • flavivirus;
  • recombinant subviral particle;
  • tick-borne encephalitis virus;
  • membrane fusion;
  • class II fusion;
  • fusion intermediate;
  • molecular antigenic structure;
  • epitope mapping;
  • flavivirus cross-reactivity;
  • neutralizing antibodies

Summary

The envelope proteins (E) of flaviviruses form an icosahedral cage-like structure of homodimers that cover completely the surface of mature virions and are responsible for receptor-binding and membrane fusion. Fusion is triggered by the acidic pH in endosomes which induces dramatic conformational changes of E that drive the merger of the membranes. We have identified an alternative trigger that induces the first phase of the fusion process only, but then leads to an arrest at an intermediate stage. These data suggest that the early and late stages of flavivirus fusion are differentially controlled by intersubunit and intrasubunit constraints of the fusion protein, respectively. Details of the molecular antigenic structure of the flavivirus E protein were revealed by the use of neutralization escape mutants as well as recombinant expression systems for the generation of virus-like particles. The experimental data provide evidence that each of the three domains contributing to the external face of the E protein can induce and bind neutralizing antibodies. Broadly flavivirus cross-reactive antibodies, however, primarily recognize a site involving residues of the highly conserved fusion peptide loop which is cryptic and largely inaccessible on the surface of native infectious virions.