|Peeters, Ben p|
Submitted to: Avian Diseases
Publication Type: Peer reviewed journal
Publication Acceptance Date: 6/3/2006
Publication Date: 1/3/2007
Citation: Wakamatsu, N., King, D.J., Seal, B.S., Peeters, B.H., Brown, C. 2006. The effect on pathogenesis of Newcastle disease virus LaSota strain from a mutation of fusion cleavage site to a virulent sequence. Avian Diseases. 50:483-488. Interpretive Summary: Newcastle disease virus (NDV) strains are all members of the same serotype but they cause infections of poultry that vary from being clinically inapparent to severe disease forms with high mortality. The viral genetic basis for the different clinical disease forms resulting from infections with different strains remains undefined. Infectious copies of NDV LaSota, one like the parent virus and the other like the parent except with a mutation in the fusion gene to make that locus identical to known virulent viruses, were compared with the parent virus to determine the effect of the introduced mutation on disease in infected chickens. Although the introduced mutation markedly increased the virus virulence in standard pathogenicity tests, there was only a mild increase in disease from a natural infection. Increased clinical disease severity therefore appears to involve multiple virus genes in contrast to pathogenicity test results which could be impacted by a change at only one region of a single gene.
Technical Abstract: The principal molecular determinant of virulence of Newcastle disease virus (NDV) is the amino acid sequence at the fusion cleavage activation site. To extend the understanding of the role of the fusion cleavage activation site in NDV virulence, the pathogenesis in chickens of a lentogenic LaSota isolate and two infectious clones, NDFL and NDFLtag were compared. NDFL is an infectious clone of a lentogenic NDV strain (LaSota E13-1), and NDFLtag is the infectious clone with the fusion cleavage site sequence mutated to the virulent motif, which were described by Peeters et al. (1999). The viruses were inoculated intraconjunctivally into groups of 4-week-old White Leghorn chickens and compared in a pathogenesis study for determination of disease causation (clinical signs of disease, gross lesions, histology, virus isolation, and serology) and viral distribution (presence of viral nucleoprotein and mRNA was detected by immunohistochemistry and in situ hybridization, respectively). Modifying the fusion cleavage activation site to virulent motif in the infectious clone only slightly increased disease severity and viral distribution, even though dramatically increased pathogenicity was confirmed by standard pathogenicity index tests. The result, that the mutated fusion cleavage site of NDV-NDFLtag had only a small influence on pathogenesis in chickens compared to either E13-1 or NDFL, suggests that the pathogenic effects of NDV are not dependent on the fusion cleavage site alone.