Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus

Abstract

A monoclonal antibody (MCI20.6) which inhibited measles virus (MV) binding to host cells was previously used to characterize a 57to 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 [35S5methionine. 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.

Effect of siRNA mediated suppression of signaling lymphocyte activation molecule on replication of peste des petits ruminants virus in vitro

“…Another possibility could be the possible usage of other receptors by PPRV. In case of MV, in addition to SLAM or CD150, CD46 has also been shown to play an important role in virus entry (Dorig et al, 1993;Naniche et al, 1993).…”

Bat-derived influenza-like viruses H17N10 and H18N11

“…The structures of the globular heads of HN proteins display a conserved b-sheet propeller motif, which was identified originally in influenza virus NA, and an SA binding site located in the central cavity of the proteins [39,40]. Unlike HN, the hemagglutinin (H) of measles virus (MV), which also belongs to the Paramyxoviridae family, possesses an inactivated SA receptor binding site and recognizes specific proteins, such as signal lymphocyteactivating molecule (SLAM), CD46, and nectin-4 [41][42][43]. The structure of the globular heads of H protein still reveals a conserved b-sheet propeller motif, and the specific protein receptors bind to the side part of H protein with different orientations [44].…”

Mapping the evolutionary trajectories of morbilliviruses: what, where and whither

“…When categorizing morbillivirus attributes it is essential to focus exclusively on wild-type morbillivirus strains as overarching generalizations cannot be made if vaccine viruses and laboratory-adapted strains are included since adaptation during in vitro passage in inappropriate cell lines is common. This is best illustrated by the first, and least clinically-relevant receptor identified for MV, CD46 [1,2] a cell surface molecule used in vitro by laboratory-adapted and vaccine strains but not by wild-type viruses [3]. Immunization of macaques with a recombinant (r) MV derived from the Edmonston-Zagreb (EZ) vaccine strain grown in CD46 expressing MRC-5 cells demonstrated that even though the vaccine virus uses CD46 in vitro this is not the case in vivo [4].…”