Antibody recognition of picornaviruses and escape from neutralization: a structural view

Abstract

Escape of picornaviruses from neutralization by monoclonal antibodies is mediated by substitutions of very few, defined amino acid residues of the capsid, generally located on the tip of some surface-exposed loops. Substitutions at the same positions are possibly of major relevance to antigenic variation of picornaviruses in the field. Such residues tend to cluster in discrete areas, termed antigenic sites. The structure of virus-antibody and peptide-antibody complexes, determined by cryoelectron microscopy and X-ray crystallography, combined with studies using site-directed mutagenesis, are beginning to reveal new features of picornavirus epitopes. This information complements and expands the view on picornavirus antigenicity previously provided by analyses of antibody-escape mutants. In addition to amino acids found replaced in escape mutants, other surface residues which remain invariant in spite of immune pressure also participate in contacts with the antibody molecule. Some invariant residues are even critical for the antigen-antibody interaction. Escape mutations occur at the subset of antigenically critical residues which are tolerant to change because they are not essentially involved in capsid structure or function. Restrictions to variation differ among epitopes; this may contribute to explain the different number of serotypes among picornaviruses, and the frequency at which antigenically highly divergent variants occur in the field.