Binding of measles virus to membrane cofactor protein (CD46): importance of disulfide bonds and N-glycans for the receptor function.
Two cellular proteins, membrane cofactor protein (MCP) and moesin, were reported recently to be functionally associated with the initiation of a measles virus infection. We have analyzed the interaction of measles virus with cell surface proteins, using an overlay binding assay with cellular proteins immobilized on nitrocellulose. Among surface-biotinylated proteins from a human rectal tumor cell line (HRT), measles virus was able to bind only to a 67-kDa protein that was identified as MCP. The virus recognized different isoforms of MCP expressed from human (HRT and HeLa) and simian (Vero) cell lines. The binding of measles virus to MCP was abolished after cleavage of the disulfide bonds by reducing agents as well as after enzymatic release of N-linked oligosaccharides. By contrast, removal of sialic acid or O-linked oligosaccharides did not affect the recognition of MCP measles virus. These data indicate that the receptor determinant of MCP is dependent on a conformation of the protein that is maintained by disulfide bonds and N-glycans present in the complement binding domains. Our results are consistent with a role of MCP as primary attachment site for measles virus in the initial stage of an infection. The functional relationship between MCP and moesin in a measles virus infection is discussed.
Maisner
A
A
Institut für Virologie, Philipps-Universität Marburg, Germany.
Schneider-Schaulies
J
J
Liszewski
M K
MK
Atkinson
J P
JP
Herrler
G
G
D000818:Animals; D015703:Antigens, CD / Q000302:isolation & purification / Q000378:metabolism*; D001710:Biotin; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002522:Chlorocebus aethiops; D004220:Disulfides; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D008459:Measles virus / Q000302:isolation & purification / Q000378:metabolism*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D009844:Oligosaccharides / Q000302:isolation & purification / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D012004:Rectal Neoplasms; D012794:Sialic Acids; D014407:Tumor Cells, Cultured; D014709:Vero Cells
D015703:Antigens, CD; C497857:CD46 protein, human; D004220:Disulfides; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D011134:Polysaccharides; D012794:Sialic Acids; D001710:Biotin