NEUTRALIZING ANTIBODY TO HUMAN RHINOVIRUS-14 PENETRATES THE RECEPTOR-BINDING CANYON

THE three-dimensional structure of intact human rhinovirus 14 (HRV-14) complexed with Fab fragments (Fab17-IA) from a strongly neutralizing antibody that binds bivalently to the virion(1,2) has been determined to 4.0 Angstrom resolution by a combination of X-ray crystallography a nd cryo-electron microscopy. In contradiction to the most commonly hel d model of antibody-mediated neutralization, Fab17-IA does not induce a conformational change in the HRV-14 capsid. Instead, the paratope of the antibody undergoes a large conformational change to accommodate t he epitope. Unlike any previously described antibody-antigen structure , the conserved framework region of the antibody makes extensive conta ct with the viral surface. Fab17-IA penetrates deep within the canyon in which the cellular receptor for HRV-14 binds(3,4). Hence, it is unl ikely that viral quaternary structure evolves merely to evade immune r ecognition, Instead, the shape and position of the receptor-binding re gion on a virus probably dictates receptor binding and subsequent unco ating events and has little or no influence on concealing the virus fr om the immune system.