Role of individual genes, genotypes and cytokines in the pathogenesis and virulence of Newcastle disease
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Newcastle disease (ND) is a limiting disease of poultry worldwide caused by virulent strains of Newcastle disease virus (NDV), and often responsible for major panzootics and extensive poultry mortality. ND requires notification to the Office of International Epizootics (OIE). Although all isolates of NDV belong to the same serotype, different isolates can produce very different clinico-pathological disease in susceptible hosts. Such diversity has been imputed to the contribution of the different genes that compose the NDV genome, and to the intrinsic innate immune response of the host. In addition, recent evidence shows that numerous new genotypes of NDV are emerging, possibly further increasing the variability of ND presentation and NDV host range. Therefore, a better understanding of NDV pathogenesis should be pursued through the characterization of isolates that belong to new genotypes, and through the evaluation of the molecular pathogenesis of the disease, as determined by the viral genes and the cytokine response during viral infection. In a first set of experiments, NDV infectious clones with substitutions of the HN (hemagglutinin-neuraminidase) and F (fusion) genes or the insertion of chicken Interferon Gamma (IFN-) were rescued by reverse genetic techniques, and were tested in 4-week-old chickens. Results showed that mere substitution of HN and F belonging to virulent viruses did not significantly increase virulence when inserted into a low virulence backbone; whereas insertion of IFN- into a virulent backbone markedly decreased its virulence. Furthermore, results showed that addition of extra genes within the viral backbone decreased the overall virulence, but enhanced the neurotropic behavior of NDV. In another set of experiments, three wild type strains from recent outbreaks and belonging to newly described genotypes were characterized in pathogenesis experiments to assess possible changes in pathogenicity. Results showed that tested strains acted similarly to what was previously observed, with a marked tropism for lymphoid tissues. Strain belonging to genotype I, class II (Australia strain) had attenuated pathogenicity, which was unexpected based on the results of standard pathogenicity indices. This underscores the importance of animal experimentation to completely characterize newly isolated NDV genotypes.