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, wer e reported recently to be functionally associated with the initiation of a measles virus infection. We have analyzed the interaction of meas les virus with cell surface proteins, using an overlay binding assay w ith cellular proteins immobilized on nitrocellulose. Among surface-bio tinylated 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 hu man (HRT and HeLa) and simian (Vero) cell lines. The binding of measle s virus to MCP was abolished after cleavage of the disulfide bonds by reducing agents as well as after enzymatic release of N-linked oligosa ccharides. By contrast, removal of sialic acid or O-linked oligosaccha rides did not affect the recognition of MCP by measles virus. These da ta indicate that the receptor determinant of MCP is dependent on a con formation of the protein that is maintained by disulfide bonds and N-g lycans present in the complement binding domains. Our results are cons istent with a role of MCP as primary attachment site for measles virus in the initial stage of an infection. The functional relationship bet ween MCP and moesin in a measles virus infection is discussed.