Interaction of Major Group Rhinoviruses with Their Cellular Receptor, ICAM-1

Abstract

The first step in the virus life cycle is the interaction between the virus and the cellular receptor. This interaction is a significant determinant of pathogenesis. For picornaviruses, the best studied virus-receptor interaction has been that of the major group rhinoviruses and their cellular receptor, intercellular adhesion molecule-1 (ICAM-1, CD54). Later, following the structure determination of rhinovirus, the receptor for the major group of rhinoviruses was identified as ICAM-1. It should be informative to examine the features of a receptor and a virus that use this canyon strategy for attachment and entry. This chapter looks at a well-studied example of this interaction at a structural level, the interaction of the major group rhinoviruses with their cellular receptor, ICAM-1. Molecular genetic and structural studies have demonstrated that rhinoviruses bind to domain D1 of ICAM-1. A major tenet of the canyon hypothesis suggested that the receptor would bind in the crevice that surrounds each of the fivefold vertices. This was supported by molecular genetic studies in which residues that line the floor of the canyon in rhinovirus 14 (HRV14) were mutated and the resulting virus particles had altered levels of receptor binding. The electron density values for D1D2 were nearly identical to those of the virus, indicating a nearly complete saturation of all of the 60 available binding sites on the virion. The association of ICAM-1 with HRV3 was slow compared with other protein-protein interactions, suggesting that the receptor may have a difficult time penetrating the canyon and making the correct contacts.