Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus.
A monoclonal antibody (MCI20.6) which inhibited measles virus (MV) binding 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 amino acid sequencing identified it as human membrane cofactor protein (CD46), a member of the regulators of complement activation gene cluster. Transfection of nonpermissive murine cells with a recombinant expression vector containing CD46 cDNA conferred three major properties expected 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 hemagglutinin and MV fusion glycoproteins were expressed after infection with a vaccinia virus recombinant encoding both MV glycoproteins. Third, M12.CD46 murine B cells were able to support MV replication, as shown by production of infectious virus and by cell biosynthesis of viral hemagglutinin after metabolic labeling of infected cells with [35S]methionine. These results show that the human CD46 molecule serves as an MV receptor allowing virus-cell binding, fusion, and viral replication and open new perspectives in the study of MV pathogenesis.
CNRS-ENS-Lyon UMR 49, France.
D
D
Naniche
G
G
Varior-Krishnan
F
F
Cervoni
T F
TF
Wild
B
B
Rossi
C
C
Rabourdin-Combe
D
D
Gerlier
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D001402:B-Lymphocytes; D002459:Cell Fusion / Q000502:physiology; D002460:Cell Line; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D007739:L Cells; D008459:Measles virus / Q000502:physiology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes; D014162:Transfection; D014709:Vero Cells
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D011994:Recombinant Proteins