Alan Mcclelland

The major human rhinovirus receptor is ICAM-1

The major human rhinovirus receptor has been identified with monoclonal antibodies that inhibit rhinovirus infection. These monoclonal antibodies recognize a 95 kd cell surface glycoprotein on human cells and on mouse transfectants expressing a rhinovirus binding phenotype. Purified 95 kd protein binds to rhinovirus in vitro. Protein sequence from the 95 kd protein showed an identity with that of intercellular adhesion molecule-1 (ICAM-1); a cDNA clone obtained from mouse transfectants expressing the rhinovirus receptor had essentially the same sequence as ICAM-1. Thus, the major human rhinovirus receptor is ICAM-1. The gene for this receptor maps to human chromosome 19, which also contains the genes for a number of other picornavirus receptors.

Preliminary X-ray crystallographic analysis of intercellular adhesion molecule-1☆

Abstract Crystals of the two ammo-terminal domains of intercellular adhesion molecule-1, the receptor for the major group of human rhinovirus serotypes, diffract to 3.0 Å resolution. The crystals are trigonal in space group P3121 or P3221 with cell dimensions of a = b = 55.7 A ̊ , c = 166.3 A ̊ , with probably six molecules per unit cell.

[25] Molecular cloning of receptor genes by transfection

Summary We have described a transfection method for the isolation of surface antigen genes which requires no mRNA or protein purification. Application of this technique results in the recovery of the entire gene in a single step since selection for expression of genomic DNA forms the basis of the procedure. Based on our results with the transferrin receptor gene and other systems it is evident that large transcription units can be transferred and expressed in mouse L-cells. This size consideration represents a major advantage over the use of cosmid shuttle vectors for genomic DNA expression. In the case of genes which code for very long mRNAs this method may also have advantages over cDNA expression systems. Although we have described methods for FACS isolation of transfectants based on the binding of species specific antibodies to surface antigens, other methods of identifying transfected cells could be employed. For example, in combination with an appropriate assay, sib selection of recipient cells could be used to identify genes encoding secreted products. Ligand binding assays could be used for receptors which are not expressed on the host cell. Finally, the development of cDNA expression vectors which produce membrane-associated products would extend this methodology to genes not normally expressed at the cell surface.

Structure of a human Rhinovirus complexed with its receptor molecule

INTRODUCTION. Human rhinoviruses are one of the major causes of the common cold. They, like other picornaviruses, are icosahedral assemblies of 60 protomers that envelope a single, positive-sense strand of RNA. Each protomer consists of four polypeptides, VPl VP4. The three external viral proteins (VPl VP3) each have an approximate molecular weight of 30,000 and a similar folding topology 0,2). The external viral radius is -150 A and the total molecular weight is roughly 8.5 x 106. A surface depression, or canyon, that is about 12 A deep and 12 -15 A wide, encircles each pentagonal vertex. Residues lining the canyon are more conserved than other surface residues among rhinovirus serotypes (3). The most variable surface residues are at the sites of attachment of neutralizing antibodies 0,5). It has been proposed that the cellular receptor molecule recognized by the virus binds to conserved residues in the canyon, thus escaping neutralization by host antibodies that are too big to penetrate into that region. This hypothesis 0,6) is supported by site-directed mutagenesis of residues lining the canyon which alters the ability of the virus to attach to HeLa cell membranes (7). Also, conformational changes in the floor of the canyon, produced by certain antiviral ageflts that bind into a pocket beneath the canyon flooT, inhibit viral attachment to cellular membranes (8). Conservation of the viral attachment site inside a surface depression has been observed for Mengo (9) and influenza virus (10).