Emergence of Novel Human Norovirus GII.17 Strains Correlates With Changes in Blockade Antibody Epitopes

J Infect Dis. 2017 Dec 5;216(10):1227-1234. doi: 10.1093/infdis/jix385.

Abstract

Background: Human norovirus is a significant public health burden, with >30 genotypes causing endemic levels of disease and strains from the GII.4 genotype causing serial pandemics as the virus evolves new ligand binding and antigenicity features. During 2014-2015, genotype GII.17 cluster IIIb strains emerged as the leading cause of norovirus infection in select global locations. Comparison of capsid sequences indicates that GII.17 is evolving at previously defined GII.4 antibody epitopes.

Methods: Antigenicity of virus-like particles (VLPs) representative of clusters I, II, and IIIb GII.17 strains were compared by a surrogate neutralization assay based on antibody blockade of ligand binding.

Results: Sera from mice immunized with a single GII.17 VLP identified antigenic shifts between each cluster of GII.17 strains. Ligand binding of GII.17 cluster IIIb VLP was blocked only by antisera from mice immunized with cluster IIIb VLPs. Exchange of residues 393-396 from GII.17.2015 into GII.17.1978 ablated ligand binding and altered antigenicity, defining an important varying epitope in GII.17.

Conclusions: The capsid sequence changes in GII.17 strains result in loss of blockade antibody binding, indicating that viral evolution, specifically at residues 393-396, may have contributed to the emergence of cluster IIIb strains and the persistence of GII.17 in human populations.

Keywords: GII.17; Norovirus; antibody neutralization; blockade antibody; viral evolution.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Antibodies, Blocking / chemistry
  • Antibodies, Blocking / immunology*
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / immunology*
  • Antigenic Variation
  • Caliciviridae Infections / epidemiology
  • Caliciviridae Infections / immunology*
  • Caliciviridae Infections / virology*
  • Capsid Proteins / chemistry
  • Capsid Proteins / immunology
  • Disease Models, Animal
  • Epitopes / chemistry
  • Epitopes / immunology
  • Genetic Variation
  • Guinea Pigs
  • Humans
  • Immunization
  • Mice
  • Models, Molecular
  • Norovirus / classification
  • Norovirus / genetics
  • Norovirus / immunology*
  • Norovirus / ultrastructure
  • Protein Binding
  • Protein Conformation
  • Rabbits

Substances

  • Antibodies, Blocking
  • Antibodies, Viral
  • Capsid Proteins
  • Epitopes