Amino acid substitutions at position 481 differently affect the ability ofthe measles virus hemagglutinin to induce cell fusion in monkey and marmoset cells co-expressing the fusion protein

The hemagglutinin (H) protein of the measles virus (MV) Edmonston strain in duced cell fusion in Cos (monkey) and B95a (marmoset) cells, when co-expres sed with the fusion (F) protein, whereas the H protein of the wild-type KA strain induced fusion in B95a cells, but not in Cos cells. Asparagine resid ue at position 481 of the KA H protein was replaced by various amino acids through site-directed mutagenesis. Substitution with tyrosine, which was fo und at position 481 of the Edmonston H protein, enabled the mutant KA H pro tein (N481Y) to induce cell fusion in Cos cells co-expressing the F protein , which could be completely blocked by anti-CD46 antibody. This mutant, how ever, did not cause CD46 downregulation, unlike the Edmonston H protein. Th e other H protein mutants (N481S, N481T, N481D, N481H, N481F) did not produ ce syncytia in Cos cells. On the other hand, all of the mutants retained th e ability to induce cell fusion in B95a cells. Thus, while tyrosine at posi tion 481 was indispensable for the MV H protein's interaction with CD46, th e residue at this position does not appear to be critically involved in the interaction with the receptor for wild-type strains present on B95a cells.