FUNCTIONAL AND STRUCTURAL INTERACTIONS BETWEEN MEASLES-VIRUS HEMAGGLUTININ AND CD46

We analyzed the roles of the individual measles virus (MV) surface gly coproteins in mediating functional and structural interactions with hu man CD46, the primary MV receptor. On one cell population, recombinant vaccinia virus vectors were used to produce the MV hemagglutinin (II) and fusion (F) glycoproteins. As fusion partner cells, various cell t ypes were examined, without or with human CD46 (endogenous or recombin ant vaccinia virus encoded), Fusion between the two cell populations w as monitored by a quantitative reporter gene activation assay and by s yncytium formation, MV glycoproteins promoted fusion with primate cell s but not with nonprimate cells; recombinant CD46 rendered nonprimate cells competent for MV glycoprotein-mediated fusion, Markedly differen t fusion specificity was observed for another morbillivirus, canine di stemper virus (CDV): recombinant CDV glycoproteins promoted fusion wit h primate and nonprimate cells independently of CD46. Fusion by the re combinant MV and CDV glycoproteins required coexpression of H plus F i n either homologous or heterologous combinations. To assess the role o f H versus F in determining the CD46 dependence of MV fusion, we exami ned the fusion specificities of cells producing heterologous glycoprot ein combinations, The specificity of H-MV plus F-CDV paralleled that o bserved for the homologous MV glycoproteins: fusion occurred with prim ate cells but not with nonprimate cells unless they produced recombina nt CD46. By contrast, the specificity of H-CDV plus F-MV paralleled th at for the homologous CDV glycoproteins: fusion occurred with either p rimate or nonprimate cells with no dependence on CD46. Thus, for both MV and CDV; fusion specificity was determined by H. In particular, the results demonstrate a functional interaction between H-MV and CD46, F low cytometry and antibody coprecipitation studies provided a structur al correlate to this functional interation: CD46 formed a molecular co mplex with H-MV but not with F-MV or with either CDV glycoprotein. The se results highlight the critical role of the H glycoprotein in determ ining MV spectificity for CD46-positive cells.