O. Nussbaum et al., FUNCTIONAL AND STRUCTURAL INTERACTIONS BETWEEN MEASLES-VIRUS HEMAGGLUTININ AND CD46, Journal of virology, 69(6), 1995, pp. 3341-3349
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.