Discrimination among rhinovirus serotypes for a variant ICAM-1 receptor molecule

Intercellular adhesion molecule 1 (ICAM-1) is the cellular receptor for the major group of human rhinovirus serotypes, including human rhinovirus 14 (HRV14) and HRV16. A naturally occurring variant of ICAM-1, ICAM-1(Kilifi), has altered binding characteristics with respect to different HRV serotypes. HRV14 binds to ICAM-1 only transiently at physiological temperatures but forms a stable complex with ICAM-1(Kilifi). Conversely, HRV16 forms a stable complex with ICAM-1 but does not bind to ICAM-1(Kilifi). The three-dimensional structures of HRV14 and HRV16, complexed with ICAM-1, and the structure of HRV14, complexed with ICAM-1(Kilifi), have been determined by cryoelectron microscopy (cryoEM) image reconstruction to a resolution of approximately 10 Angstrom. Structures determined by X-ray crystallography of both viruses and of ICAM-1 were fitted into the cryoEM density maps. The interfaces between the viruses and receptors contain extensive ionic networks. However, the interactions between the viruses and ICAM-1(Kilifi) contain one less salt bridge than between the viruses and ICAM-1. As HRV16 has fewer overall interactions with ICAM-1 than HRV14, the absence of this charge interaction has a greater impact on the binding of ICAM-1(Kilifi) to HRV16 than to HRV14.