ICAM-1 receptors and cold viruses

Bella, Jordi; Rossmann, Michael G.

Human rhinoviruses (HRVs), the single most important etiologic agent of common colds, are small viruses composed of an icosahedral protein shell that encapsidates a single, positive RNA strand. Multiplication of HRVs occurs in the cytoplasm of the host cell. To produce infection, HRVs must first attach to specific cellular receptors embedded in the plasma membrane. Ninety percent of HRVs immunogenic variants use as receptor intercellular adhesion molecule-1 (ICAM-1), a cell surface glycoprotein that promotes intercellular signaling in processes derived from inflammation response. As HRV receptor, ICAM-1 positions the virus to within striking distance of the membrane, and then triggers a conformational change in the virus that ultimately results in delivery of the viral RNA genome into the cytoplasm, across a lipid bilayer. The interaction between ICAM-1 and HRVs has been analyzed by the combination of crystal structures of HRVs and ICAM-1 fragments with electron microscopy reconstructions of the complexes. The resulting molecular models are useful to address questions about receptor recognition, binding specificity, and mechanisms by which ICAM-1 induces virus uncoating.