Physical association of moesin and CD46 as a receptor complex for measles virus.
Recently, two cellular membrane proteins, the membrane cofactor protein CD46 and the membrane-organizing external spike protein, moesin, have 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 combined on MV attachment, fusion, and plaque formation and the putative direct physical interaction of moesin and CD46. We found that antibodies to moesin or CD46 separately inhibited MV-cell interactions to a high percentage in the plaque test, by approximately 85 and 75%, respectively. 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. Furthermore, antimoesin antibodies blocked the infection of CD46-negative mouse cell lines with MV. Chemical cross-linking of cell surface proteins indicated the close proximity of CD46 and moesin in the membrane of human cells, and coimmunoprecipitation of moesin with CD46 suggested their physical interaction. Immunohistochemically by electron microscopy, CD46 and moesin were found to be localized at sites of the cellular 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 MV into cells.
Schneider-Schaulies
J
J
Institut für Virologie und Immunbiologie, Würzburg, Germany.
Dunster
L M
LM
Schwartz-Albiez
R
R
Krohne
G
G
ter Meulen
V
V
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D003432:Cross-Linking Reagents; D006801:Humans; D007150:Immunohistochemistry; D008459:Measles virus / Q000378:metabolism*; D051916:Membrane Cofactor Protein; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D011233:Precipitin Tests; D011506:Proteins / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D011991:Receptors, Virus / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D010948:Viral Plaque Assay
D015703:Antigens, CD; C497857:CD46 protein, human; D003432:Cross-Linking Reagents; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D011506:Proteins; D011991:Receptors, Virus; C071058:moesin