Formation of rhinovirus-soluble ICAM-1 complexes and conformational changes in the virion.
Viral receptors serve both to target viruses to specific cell types and to actively promote the entry of bound virus into cells. Human rhinoviruses (HRVs) can form complexes in vitro with a truncated soluble form of the HRV cell surface receptor, ICAM-1. These complexes appear to be stoichiometric, with approximately 60 ICAM molecules bound per virion or 1 ICAM-1 molecule per icosahedral face of the capsid. The complex can have two fates, either dissociating to yield free virus and free ICAM-1 or uncoating to break down to an 80S empty capsid which has released VP4, viral RNA, and ICAM-1. This uncoating in vitro mimics the uncoating of virus during infection of cells. The stability of the virus-receptor complex is dependent on temperature and the rhinovirus serotype. HRV serotype 14 (HRV14)-ICAM-1 complexes rapidly uncoat, HRV16 forms a stable virus-ICAM complex which does not uncoat detectably at 34 degrees C, and HRV3 has an intermediate phenotype. Rhinovirus can also uncoat after exposure to mildly acidic pH. The sensitivities of individual rhinovirus serotypes to ICAM-1-mediated virus uncoating do not correlate with uncoating promoted by incubation at low pH, suggesting that these two means of virus destabilization occur by different mechanisms. Soluble ICAM-1 and low pH do not act synergistically to promote uncoating. The rate of uncoating does appear to be inversely related to virus affinity for its receptor.
Hoover-Litty
H
H
Institute for Molecular Biologicals, Miles Research Center, West Haven, Connecticut 06516-4175.
Greve
J M
JM
D002213:Capsid / Q000378:metabolism; D036022:Capsid Proteins; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D014644:Genetic Variation; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018799:Intercellular Adhesion Molecule-1; D046911:Macromolecular Substances; D008954:Models, Biological; D008968:Molecular Conformation; D012367:RNA, Viral / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D012229:Rhinovirus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D014771:Virion / Q000187:drug effects / Q000378:metabolism*
D036022:Capsid Proteins; D015815:Cell Adhesion Molecules; D046911:Macromolecular Substances; D012367:RNA, Viral; D011991:Receptors, Virus; C060339:VP4 protein, Rotavirus; D018799:Intercellular Adhesion Molecule-1