We sought proof of principle that one of the safest human vaccines, measles
virus Edmonston B (MV-Edm), can be genetically modified to allow entry via
cell surface molecules other than its receptor CD46. Hybrid proteins consi
sting of the epidermal growth factor (EGF) or the insulin-like growth facto
r 1 (IGF1) linked to the extracellular (carboxyl) terminus of the MV-Edm at
tachment protein hemagglutinin (H) were produced. The standard H protein ge
ne was replaced by one coding for H/EGF or H/IGF1 in cDNA copies of the MV
genome. Recombinant viruses were rescued and replicated to titers approachi
ng those of the parental strain. MV displaying EGF or IGF1 efficiently ente
red CD46-negative rodent cells expressing the human EGF or the IGF1 recepto
r, respectively, and the EGF virus caused extensive syncytium formation and
cell death. Taking advantage of a factor Xa protease recognition site engi
neered in the hybrid H proteins, the displayed domain was cleaved off from
virus particles, and specific entry in rodent cells was abrogated. These st
udies prove that MV can be engineered to selectively eliminate cells expres
sing a targeted receptor and provide insights into the mechanism of MV entr
y.