High flavivirus structural plasticity demonstrated by a non-spherical morphological variant

Nat Commun. 2020 Jun 19;11(1):3112. doi: 10.1038/s41467-020-16925-y.

Abstract

Previous flavivirus (dengue and Zika viruses) studies showed largely spherical particles either with smooth or bumpy surfaces. Here, we demonstrate flavivirus particles have high structural plasticity by the induction of a non-spherical morphology at elevated temperatures: the club-shaped particle (clubSP), which contains a cylindrical tail and a disc-like head. Complex formation of DENV and ZIKV with Fab C10 stabilize the viruses allowing cryoEM structural determination to ~10 Å resolution. The caterpillar-shaped (catSP) Fab C10:ZIKV complex shows Fabs locking the E protein raft structure containing three E dimers. However, compared to the original spherical structure, the rafts have rotated relative to each other. The helical tail structure of Fab C10:DENV3 clubSP showed although the Fab locked an E protein dimer, the dimers have shifted laterally. Morphological diversity, including clubSP and the previously identified bumpy and smooth-surfaced spherical particles, may help flavivirus survival and immune evasion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aedes
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Viral / immunology
  • Antibodies, Viral / metabolism*
  • Cell Line
  • Cryoelectron Microscopy
  • Dengue / immunology
  • Dengue / therapy
  • Dengue / virology
  • Dengue Vaccines / immunology
  • Dengue Virus / immunology
  • Dengue Virus / metabolism
  • Dengue Virus / ultrastructure*
  • Immune Evasion
  • Immunoglobulin Fab Fragments / immunology
  • Immunoglobulin Fab Fragments / metabolism
  • Mesocricetus
  • Protein Multimerization
  • Surface Properties
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism*
  • Viral Envelope Proteins / ultrastructure
  • Virus Attachment
  • Zika Virus / immunology
  • Zika Virus / metabolism
  • Zika Virus / ultrastructure*
  • Zika Virus Infection

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Dengue Vaccines
  • Immunoglobulin Fab Fragments
  • Viral Envelope Proteins