Antibodies that block rhinovirus attachment map to domain 1 of the major group receptor.
The vast majority of human rhinovirus serotypes utilize the intercellular adhesion molecule 1 (ICAM-1) as the attachment site on susceptible cells. Twelve murine monoclonal antibodies were isolated and shown by competition binding studies to recognize three distinct, nonoverlapping epitopes on the ICAM-1 receptor. Titration of three antibodies representing each of the binding sites demonstrated that they were equally effective at blocking viral attachment. By using in vitro transcription and translation systems, a series of progressive C-terminal truncations of ICAM-1 molecules was generated. Immunoprecipitation of these fragments with each of the three antibodies indicated that all three epitopes reside within the first 82 amino acids of the receptor. Attempts to demonstrate specific binding of these in vitro-synthesized receptor fragments to virions were unsuccessful. The inability to show virion binding was most likely due to a failure of the lysates to properly glycosylate the receptor molecule, since native, unglycosylated receptor molecules isolated from cell membranes were also inactive in virus binding assays.
Lineberger
D W
DW
Department of Virus and Cell Biology, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
Graham
D J
DJ
Tomassini
J E
JE
Colonno
R J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000936:Antigen-Antibody Complex; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011991:Receptors, Virus / Q000276:immunology / Q000502:physiology*; D015183:Restriction Mapping; D012229:Rhinovirus / Q000276:immunology / Q000502:physiology*; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015815:Cell Adhesion Molecules; D015345:Oligonucleotide Probes; D011991:Receptors, Virus; D018799:Intercellular Adhesion Molecule-1