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 of syncytium formation varies among different strains and correlates with the degree of viral attenuation. In this study, we examined the determinants for the differential fusogenicity of the wild-type CDV isolate 5804Han89 (CDV₅₈₀₄), the small- and large-plaque-forming variants of the CDV vaccine strain Onderstepoort (CDV_OS and CDV_OL, respectively), and the MV vaccine strain Edmonston B (MV_Edm). The cotransfection of different combinations of fusion (F) and hemagglutinin (H) genes in Vero cells indicated that the H protein is the main determinant of fusion efficiency. To verify the significance of this observation in the viral context, a reverse genetic system to generate recombinant CDVs was established. This system is based on a plasmid containing the full-length antigenomic sequence of CDV_OS. The coding regions of the H proteins of all CDV strains and MV_Edm, were introduced into the CDV and MV genetic backgrounds, and recombinant viruses rCDV-H₅₈₀₄, rCDV-H_OL, rCDV-H_Edm, rMV-H₅₈₀₄, rMV-H_OL, and rMV-H_OS were recovered. Thus, the H proteins of the two morbilliviruses are interchangeable and fully functional in a heterologous complex. This is in contrast with the glycoproteins of other members of the family Paramyxoviridae, which do not function efficiently with heterologous partners. The fusogenicity, growth characteristics, 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 used.