The hemagglutinin of canine distemper virus determines tropism and cytopathogenicity

Canine distemper virus (CDV) and measles virus (MV) cause severe illnesses in their respective hosts. The viruses display a characteristic cytopathic effect by forming syncytia in susceptible cells, For CDV, the proficiency o f syncytium formation varies among different strains and correlates with th e degree of viral attenuation. In this study, we examined the determinants for the differential fusogenicity of the wild-type CDV isolate 5804Han89 (C DV5804), the small- and large-plaque-forming variants of the CDV vaccine st rain Onderstepoort (CDV,, and CDV,,, respectively), and the MV vaccine stra in Edmonston B (MVEdm). The cotransfection of different combinations of fus ion (F) and hemagglutinin (H) genes in Vero cells indicated that the H prot ein is the main determinant of fusion efficiency. To verify the significanc e of this observation in the viral context, a reverse genetic system to gen erate recombinant CDVs was established. This system is based on a plasmid c ontaining the full-length antigenomic sequence of CDV,,. The coding regions of the I-I proteins of all CDV strains and MV,,, were introduced into the CDV and MV genetic backgrounds, and recombinant viruses rCDV-H-5804, rCDV-H -OL, rCDV-H-Edm, rMV-H-5804, rMV-H-OL, and rMV-H-OS, were recovered. Thus, the H proteins of the two morbilliviruses are interchangeable and fully fun ctional in a heterologous complex. This is in contrast with the glycoprotei ns of other members of the family Paramyxoviridae, which do not function ef ficiently with heterologous partners. The fusogenicity, growth characterist ics, and tropism of the recombinant viruses were examined and compared with those of the parental strains. All these characteristics were found to be predominantly mediated by the H protein regardless of the viral backbone us ed.