title: Mapping amino acids of the measles virus hemagglutinin responsible for receptor (CD46) downregulation.
abstract: We compared the amino acid sequences of groups of receptor (CD46) downregulating and nondownregulating measles virus (MV) hemagglutinins (Hs) and identified seven group-specific differences as candidates for the mediation of the observed differential effects. Using site-directed mutagenesis, we mutated the chosen amino acids of the H of MV-strain WTF (WTF-H), a nondownregulating H, and Introduced the corresponding amino acids of Edmonston-H (Edm-H), a downregulating H. We identified four amino acids, 211G, 243R, 451V, and 481Y, which influenced the downregulative function when introduced into WTF-H. The double mutation 451V and 481Y in WTF-H led to a degree of CD46 downregulation comparable to that of Edm-H. Conversely, introducing amino acids 451E and 481N into Edm-H resulted in a loss of the downregulative function. These results indicate that these amino acids play a decisive role in the H-CD46 interaction.
authors.affiliation: Institut für Virologie und Immunbiologie, Wörzburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Bartz
authors.forename: U
authors.initials: U
authors.lastname: Brinckmann
authors.forename: L M
authors.initials: LM
authors.lastname: Dunster
authors.forename: B
authors.initials: B
authors.lastname: Rima
authors.forename: V
authors.initials: V
authors.lastname: Ter Meulen
authors.forename: J
authors.initials: J
authors.lastname: Schneider-Schaulies
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D001665:Binding Sites; D015536:Down-Regulation; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008459:Measles virus / Q000378:metabolism*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011991:Receptors, Virus / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D006389:Hemagglutinins, Viral; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; C032397:hemagglutinin protein G, measles virus