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Virulence of Newcastle disease virus is determined by the cleavage site of the fusion protein and by both the stem region and globular head of the haemagglutinin–neuraminidase protein

¹ Wageningen University and Research Centre, Animal Sciences Group, Division of Infectious Diseases, 8200 AB Lelystad, The Netherlands
² Central Institute for Animal Disease Control, PO Box 2004, 8203 AA Lelystad, The Netherlands

Correspondence
Ben P. H. Peeters
ben.peeters{at}wur.nl

Virulence of Newcastle disease virus (NDV) is mainly determined by the amino acid sequence surrounding the fusion (F) protein cleavage site, since host proteases that cleave the F protein of virulent strains are present in more tissues than those that cleave the F protein of non-virulent strains. Nevertheless, comparison of NDV strains that carry exactly the same F protein cleavage site shows that significant differences in virulence still exist. For instance, virulent field strain Herts/33 with the F cleavage site ¹¹²RRQRRF¹¹⁷ had an intracerebral pathogenicity index of 1·88 compared with 1·28 for strain NDFLtag, which has the same cleavage site. This implies that additional factors contribute to virulence. After generating an infectious clone of Herts/33 (FL-Herts), we were able to map the location of additional virulence factors by exchanging sequences between FL-Herts and NDFLtag. The results showed that, in addition to the F protein cleavage site, the haemagglutinin–neuraminidase (HN) protein also contributed to virulence. The effect of the HN protein on virulence was most prominent after intravenous inoculation. Interestingly, both the stem region and the globular head of the HN protein seem to be involved in determining virulence.

The GenBank/EMBL/DDBJ accession number of the sequence determined in this work is AY741404.

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