Effect of mutations at the residues R25, D27, P69, and N70 of B95a-MCP on receptor activities for the measles viruses Nagahata wild-type strain and CAM vaccine strain.

Abstract

Human membrane cofactor protein (MCP, CD46) is a regulator of complement activation and also serves as a receptor for measles virus (MV). We recently isolated an MCP homolog from B95a, an Epstein-Barr virus-transformed marmoset B-lymphoblastoid cell line, which is 76% identical to human-MCP. B95a-MCP acts as an MV receptor for CAM, a vaccine strain of MV, but not for Nagahata, wild-type MV strain. The four residues in human-MCP (Asp27, Lys29, Arg69, and Asp70) are reportedly MV binding sites, and these are changed in B95a-MCP (Glu27, Asp29, Pro69, and Asn70). In the present study, we constructed B95a-MCP mutants by replacing the four residues with those in human-MCP, and tested whether the Chinese hamster ovary (CHO) transfectants expressing B95a-MCP mutants become susceptible to the Nagahata strain. The CHO transfectants expressing B95a-MCP mutants formed syncytium with the CAM strain but not with the Nagahata strain. The binding of the hemagglutinin (H) of MV with B95a-MCP mutants was observed with the CAM strain but not with the Nagahata strain. These results suggest that the failure of B95a-MCP as the MV receptor for the Nagahata strain is not due simply to the natural mutations at these four residues. The critical residues for MV binding in an MCP molecule seem to differ depending upon the structure of the MV H protein.