BLOCKING MEASLES-VIRUS INFECTION WITH A RECOMBINANT SOLUBLE FORM OF, OR MONOCLONAL-ANTIBODIES AGAINST, MEMBRANE COFACTOR PROTEIN OF COMPLEMENT (CD46)

Human membrane cofactor protein (MCP, CD46) functions as an inhibitor of the complement (C) cascade to protect host cells from C attack, and as a receptor for measles virus (MV). Normal human sera contains 10-6 0 ng/ml of naturally produced soluble forms of MCP, which is also a co factor for the factor I-mediated inactivation of C3b. We produced mono clonal antibodies (mAb) against MCP and a recombinant soluble form of MCP similar to the natural soluble forms, and tested their ability to block MV infection. Vero cells and CHO cells expressing human MCP were the targets. Of the antibodies tested, M75 and M177, which blocked th e C regulatory activity of MCP, efficiently blocked MV infection. More than 50 mu g/ml of the soluble form moderately blocked MV infection o f CHO cells expressing MCP, but barely blocked that of Vero cells. The two mAb and the soluble form also inhibited MV H protein-mediated gre en monkey erythrocyte rosette formation. A quantitative analysis sugge sted that 30 mu g/ml of the soluble form functionally corresponded to 0.2 mu g/ml of M177 or M75. These data established that the C regulato ry function and the MV receptor function of MCP were blocked simultane ously by the individual mAb, and that soluble forms of MCP could inhib it MV infection in cells expressing human MCP, although doses far high er than the natural concentration of soluble MCP were required.