Abstract
BackgroundThe strains of the genotype VIId Newcastle disease virus (NDV) induce more severe tissue damage in lymphoid organs than other virulent strains. The underlying molecular mechanisms are poorly understood.MethodsGenotype IV NDV Herts/33 and genotype VIId NDV JS5/05 have a distinctive pathological profile in the spleen. These two strains of viruses were selected as parental viruses to generate a panel of chimeric viruses by replacing the M, F and HN genes of Herts/33 individually or in combination with the corresponding genes of JS5/05 using reverse genetic. Virulence and in vitro characteristics of the recombinant viruses were assessed. In addition, pathological changes, virus load, and transcriptional cytokine response in the spleen of chickens infected with these recombinant viruses were also analyzed.ResultsPathogenicity test showed that all chimeric viruses are virulent. In vitro characterization revealed that gene replacement did not change growth kinetics and HN expression on cell surface of the recombinant viruses. However, replacement of the M, F and HN genes resulted in apparent changes in the fusion activity. Moreover, pathological studies revealed that only inclusion of the homologous M, F and HN genes of JS5/05 in Herts/33 backbone resulted in severe pathological changes characterized by extensive necrosis in the spleen, similar to that induced by JS5/05. In addition, this gene replacement significantly increased virus replication and the levels of transcriptional cytokine response, compared to Herts/33. Conversely, inclusion of the M, F and HN genes of Herts/33 into JS5/05 backbone resulted in Herts/33-specific pathological changes and significantly decreased virus load and the expression levels of cytokine genes, compared to JS5/05.ConclusionsThe M, F and HN genes are related to the severe pathological changes in the spleen of chickens infected with genotype VIId NDV.
Highlights
The strains of the genotype VIId Newcastle disease virus (NDV) induce more severe tissue damage in lymphoid organs than other virulent strains
We found that Intracerebral pathogenicity index (ICPI) values of all chimeric viruses were above 1.80, and mean death time (MDT) values were lower than 60 h (Fig. 2), which are comparable to that of the parental strain, suggesting that all recombinant viruses have high virulence
Gene replacement led to slight decrease in HN expression in infected cells compared to the corresponding parental virus, but no significant difference was observed. These results showed that gene replacement did not affect HN expression on cell surface of the recombinant viruses
Summary
The strains of the genotype VIId Newcastle disease virus (NDV) induce more severe tissue damage in lymphoid organs than other virulent strains. Based on the disease severity in chickens, NDV strains are divided into three pathotypes: lentogenic, mesogenic and velogenic [1]. NDV tropism mainly depends on the virus pathotype, and generally viscerotropic velogenic strains cause severe lesions in the lymphoid system, intestinal tract and respiratory tract. Different virulent NDV strains sharing similar F cleavage site associated with high virulence induce distinct pathological manifestation in chickens, especially in lymphoid tissues [4,5,6,7]. Some recent studies have shown that some NDV isolates of genotype VIId induce more severe tissue damage in lymphoid organs compared to other virulent NDV strains [5, 6, 8]. We have provided both in vitro and in vivo data that high levels of virus replication and an intense inflammatory response contribute to this pathological manifestation of genotype VIId of NDV [8, 9]
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