Nucleotide sequence of the fusion and haemagglutinin-neuraminidase glycoprotein genes of Newcastle disease virus, strain Ulster: molecular basis for variations in pathogenicity between strains.

The nucleotide sequences of the fusion (F) and haemagglutinin-neuraminidase (HN) glycoprotein genes of the extremely avirulent Newcastle disease virus (NDV) strain Ulster have been determined by sequencing cDNA clones derived from viral genomic RNA. Open reading frames, assumed to encode the F0 and HN0 glycoprotein precursors, were 553 and 616 amino acids long, respectively. Comparisons of the two glycoprotein sequences with those of more virulent NDV strains suggested an explanation for the molecular basis of the wide-ranging differences in virulence observed between strains of NDV. The open reading frame corresponding to the Ulster HN glycoprotein extended beyond the C terminus of more virulent strains. This C-terminal extension was assumed to be responsible for the origin of the HN precursor (HN0) found in strain Ulster and other extremely avirulent strains of NDV. There were fewer basic amino acids at the cleavage site of F0 in strain Ulster than are present in more virulent strains, which may be responsible for the absence of cleavage and activation of F0 from this strain in many host cells. In more virulent strains of NDV, as well as in other paramyxoviruses, a phenylalanine residue occurs at the N terminus of the F1 cleavage fragment. The occurrence of a leucine residue at this position in strain Ulster may be partly responsible for the lack of virulence of this strain.