HUMAN MEMBRANE COFACTOR PROTEIN (CD46) ACTS AS A CELLULAR RECEPTOR FOR MEASLES-VIRUS

A monoclonal antibody (MCI20.6) which inhibited measles virus (MV) bin ding to host cells was previously used to characterize a 57- to 67-kDa cell surface glycoprotein as a potential MV receptor. In the present work, this glycoprotein (gp57/67) was immunopurified, and N-terminal a mino acid sequencing identified it as human membrane cofactor protein (CD46), a member of the regulators of complement activation gene clust er. Transfection of nonpermissive murine cells with a recombinant expr ession vector containing CD46 cDNA conferred three major properties ex pected of cells permissive to MV infection. First, expression of CD46 enabled MV to bind to murine cells. Second, the CD46-expressing murine cells were able to undergo cell-cell fusion when both MV hemagglutini n and MV fusion glycoproteins were expressed after infection with a va ccinia virus recombinant encoding both MV glycoproteins. Third, M12.CD 46 murine B cells were able to support MV replication, as shown by pro duction of infectious virus and by cell biosynthesis of viral hemagglu tinin after metabolic labeling of infected cells with [S-35]Methionine . These results show that the human CD46 molecule serves as an MV rece ptor allowing virus-cell binding, fusion, and viral replication and op en new perspectives in the study of MV pathogenesis.