STRUCTURAL STUDIES ON THE MECHANISMS OF ANTIBODY-MEDIATED NEUTRALIZATION OF HUMAN RHINOVIRUS

Antibodies represent a major component of the mammalian immunological defense against picornavirus infection. The work reviewed here examines structural details of antibody-mediated neutralization of human rhinovirus 24 (HRV14) using a combination of crystallography, molecular biology and electron microscopy. The atomic structures of the Fab fragment from a neutralizing monoclonal antibody (Fab17-LA) and HRV14 were used to interpret the similar to 25 Angstrom resolution cryo-electron microscopy structure of the Fab17-LA/HRV14 complex. While there were not any observable antibody-induced conformational changes in the HRV14 upon antibody binding, there was evidence that charge interactions dominate the paratope-epitope interface and that the intact antibody might bind bivalently across icosahedral two-fold axes. Site-directed mutagenesis results confirmed that charge interactions dominate antibody binding and electron microscopy studies on the mAb17-LA/HRV14 complex confirmed that this neutralizing antibody binds bivalently across icosahedral two-fold axes.