Conformational changes in intact dengue virus reveal serotype-specific expansion

Nat Commun. 2017 Feb 10;8:14339. doi: 10.1038/ncomms14339.

Abstract

Dengue virus serotype 2 (DENV2) alone undergoes structural expansion at 37 °C (associated with host entry), despite high sequence and structural homology among the four known serotypes. The basis for this differential expansion across strains and serotypes is unknown and necessitates mapping of the dynamics of dengue whole viral particles to describe their coordinated motions and conformational changes when exposed to host-like environments. Here we capture the dynamics of intact viral particles of two serotypes, DENV1 and DENV2, by amide hydrogen/deuterium exchange mass spectrometry (HDXMS) and time resolved Förster Resonance Energy Transfer. Our results show temperature-dependent dynamics hotspots on DENV2 and DENV1 particles with DENV1 showing expansion at 40 °C but not at 37 °C. HDXMS measurement of virion dynamics in solution offers a powerful approach to identify potential epitopes, map virus-antibody complex structure and dynamics, and test effects of multiple host-specific perturbations on viruses and virus-antibody complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Viral / immunology
  • Dengue / virology
  • Dengue Virus / chemistry*
  • Dengue Virus / genetics
  • Dengue Virus / physiology
  • Deuterium Exchange Measurement
  • Host-Pathogen Interactions
  • Humans
  • Models, Molecular
  • Molecular Conformation*
  • Protein Conformation
  • Serogroup
  • Temperature*
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism
  • Virion / chemistry*
  • Virion / genetics
  • Virion / physiology

Substances

  • Antibodies, Viral
  • Viral Envelope Proteins