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Journal of Virology, July 2001, p. 6418-6427, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6418-6427.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Hemagglutinin of Canine Distemper Virus Determines Tropism and Cytopathogenicity

Veronika von Messling,1 Gert Zimmer,2 Georg Herrler,2 Ludwig Haas,2 and Roberto Cattaneo1,*

Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905,1 and Institute of Virology, Veterinary School Hannover, 30559 Hannover, Germany2

Received 16 January 2001/Accepted 1 May 2001

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 (CDVOS and CDVOL, respectively), and the MV vaccine strain Edmonston B (MVEdm). 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 CDVOS. The coding regions of the H proteins of all CDV strains and MVEdm were introduced into the CDV and MV genetic backgrounds, and recombinant viruses rCDV-H5804, rCDV-HOL, rCDV-HEdm, rMV-H5804, rMV-HOL, and rMV-HOS 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.

* Corresponding author. Mailing address: Molecular Medicine Program, Mayo Foundation, Guggenheim 1838, 200 First St. SW, Rochester, MN 55905. Phone (507) 284-0171. Fax: (507) 266-2122. E-mail: cattaneo.roberto{at}mayo.edu.

Journal of Virology, July 2001, p. 6418-6427, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6418-6427.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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