PHYSICAL ASSOCIATION OF MOESIN AND CD46 AS A RECEPTOR COMPLEX FOR MEASLES-VIRUS

Recently, two cellular membrane proteins, the membrane cofactor protei n CD46 and the membrane-organizing external spike protein, moesin, hav e been identified to be functionally associated with measles virus (MV ) infectivity of cells. We investigated the functional consequences of binding of monoclonal antibodies to both molecules individually and c ombined on MV attachment, fusion, and plaque formation and the putativ e direct physical interaction of moesin and CD46. We found that antibo dies to moesin or CD46 separately inhibited MV-cell interactions to a high percentage in the plaque test, by approximately 85 and 75%, respe ctively. The inhibition by combinations of antibodies was additive at low concentrations and complete at high concentrations. This indicates that similar sites of interaction were blocked by steric hindrance. F urthermore, antimoesin antibodies blocked the infection of CD46-negati ve mouse cell lines with MV. Chemical cross-linking of cell surface pr oteins indicated the close proximity of CD46 and moesin in the membran e of human cells, and coimmunoprecipitation of moesin with CD46 sugges ted their physical interaction. Immunohistochemically by electron micr oscopy, CD46 and moesin were found to be localized at sites of the cel lular membrane where MV particles adsorbed. These data support a model of direct interaction of CD46 and moesin in the cellular membrane and suggest that this complex is functionally involved in the uptake of M V into cells.