Antibody-Mediated Neutralization of Human Rhinovirus 14 Explored by Means of Cryoelectron Microscopy and X-Ray Crystallography of Virus-Fab Complexes

摘要: The structures of three different human rhinovirus 14 (HRV14)-Fab complexes have been explored with X-ray crystallography and cryoelectron microscopy procedures. All antibodies bind to the NIm-IA site HRV14, which is beta-B-beta-C loop viral capsid protein VP1. Two antibodies, Fab17-IA (Fab17) Fab12-IA (Fab12), bivalently virion surface strongly neutralize infectivity whereas Fab1-IA (Fab1) aggregates weakly neutralizes virions. two classes virion-Fab clearly differ correlate observed binding neutralization differences. Fab17 Fab12 in essentially identical, tangential orientations surface, favors bidentate over icosahedral twofold axes. Fab1 binds a more radial orientation that makes unlikely. Although these antibody groups differ, nearly identical charge interactions occur at all paratope-epitope interfaces. Nucleotide sequence comparisons suggest are from same progenitor cell some differing residues contact south wall receptor canyon encircles each fivefold vertices. significant proportion region directly overlap much (intercellular adhesion molecule 1 [ICAM-1]) site. Fab1, however, does not on upper (the side facing away axes) as do Fab17. cause stabilization HRV14 against pH-induced inactivation; thus, may be mediated by invariant contacts canyon.