Interaction of measles virus (Hallé strain) with CD46: evidence that a common binding site on CD46 facilitates both CD46 downregulation and MV infection.
CD46 acts as a cellular receptor for vaccine strains of measles virus (MV). The MV/CD46 interaction-mediated by the MV attachment glycoprotein, the hemagglutinin (H)-not only facilitates infection but also induces CD46 downregulation. A conflict of opinion exists as to whether a single MVH binding site on CD46, or two separate sites, facilitates the two phenomena. To investigate this conundrum we first tested and compared a panel of CD46-specific monoclonal antibodies (mAbs) for their capacity to block both processes. One (mAb 13/42) abrogated both MV fusion and CD46 downregulation. Mutation of an amino acid (arg59 in the SCR1 of CD46) essential for the epitope of mAb 13/42 resulted in the abrogation of both CD46 downregulation and viral fusion. This strongly suggests that the same MV binding site on CD46 is responsible for both CD46 downregulation and MV infection.
Lecouturier
V
V
Unité Inserm 404, "Immunity and Vaccination,", Tour Inserm, Avenue Tony Garnier, 69365, Lyon Cedex, 07, France.
Rizzitelli
A
A
Fayolle
J
J
Daviet
L
L
Wild
F T
FT
Buckland
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D018604:Epitope Mapping; D006367:HeLa Cells; D006801:Humans; D008457:Measles / Q000517:prevention & control / Q000821:virology; D008458:Measles Vaccine / Q000378:metabolism; D008459:Measles virus / Q000378:metabolism*; D051916:Membrane Cofactor Protein; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011817:Rabbits; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014771:Virion / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D001120:Arginine