Measles virus (MV) hemagglutinin: evidence that attachment sites for MV receptors SLAM and CD46 overlap on the globular head.
Measles virus hemagglutinin (MVH) residues potentially responsible for attachment to the wild-type (wt) MV receptor SLAM (CD150) have been identified and localized on the MVH globular head by reference to a revised hypothetical structural model for MVH (www.pepscan.nl/downloads/measlesH.pdb). We show that the mutation of five charged MVH residues which are conserved among morbillivirus H proteins has major effects on both SLAM downregulation and SLAM-dependent fusion. In the three-dimensional surface representation of the structural model, three of these residues (D505, D507, and R533) align the rim on one side of the cavity on the top surface of the MVH globular head and form the basis of a single continuous site that overlaps with the 546-548-549 CD46 binding site. We show that the overlapping sites fall within the footprint of an anti-MVH monoclonal antibody that neutralizes both wt and laboratory-vaccine MV strains and whose epitope contains R533. Our study does not exclude the possibility that Y481 binds CD46 directly but suggests that the N481Y mutation of wt MVH could influence, at a distance, the conformation of the overlapping sites so that affinity to CD46 increases. The relevance of these results to present concepts of MV receptor usage is discussed, and an explanation is proposed as to why morbillivirus attachment proteins are H, whereas those from the other paramyxoviruses are HN (hemagglutinin-neuraminidase).
Molecular Basis of Paramyxovirus Entry, INSERM U404, Immunité et Vaccination, CERVI, IFR 128 Biosciences Lyon-Gerland, Lyon, France.
Nicolas
N
Massé
Michelle
M
Ainouze
Benjamin
B
Néel
T Fabian
TF
Wild
Robin
R
Buckland
Johannes P M
JP
Langedijk
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D015536:Down-Regulation; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000378:metabolism*; D006367:HeLa Cells; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D008459:Measles virus / Q000378:metabolism*; D051916:Membrane Cofactor Protein; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009500:Neutralization Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface; D011991:Receptors, Virus / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015703:Antigens, CD; C497857:CD46 protein, human; D000939:Epitopes; D006023:Glycoproteins; D006389:Hemagglutinins, Viral; D007136:Immunoglobulins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C000604059:SLAMF1 protein, human; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1