MAPPING AMINO-ACIDS OF THE MEASLES-VIRUS HEMAGGLUTININ RESPONSIBLE FOR RECEPTOR (CD46) DOWN-REGULATION

We compared the amino acid sequences of groups of receptor (CD46) down regulating and nondownregulating measles virus (MV) hemagglutinins (Hs ) and identified seven group-specific differences as candidates for th e mediation of the observed differential effects. Using site-directed mutagenesis, we mutated the chosen amino acids of the H of MV-strain W TF (WTF-H), a nondownregulating H, and introduced the corresponding am ino acids of Edmonston-H (Edm-H), a downregulating H. We identified fo ur amino acids, 211G, 243R, 451V, and 481Y, which influenced the downr egulative function when introduced into WTF-H. The double mutation 451 V 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 in to Edm-H resulted in a loss of the downregulative function. These resu lts indicate that these amino acids play a decisive role in the H-CD46 interaction. (C) 1996 Academic Press, Inc.