Abstract
Newcastle disease virus (NDV) has caused significant outbreaks in South-East Asia, particularly in Indonesia in recent years. Recently emerged genotype VII NDVs (NDV-GVII) have shifted their tropism from gastrointestinal/respiratory tropism to a lymphotropic virus, invading lymphoid organs including spleen and bursa of Fabricius to cause profound lymphoid depletion. In this study, we aimed to identify candidate genes and biological pathways that contribute to the disease caused by this velogenic NDV-GVII. A transcriptomic analysis based on RNA-Seq of spleen was performed in chickens challenged with NDV-GVII and a control group. In total, 6361 genes were differentially expressed that included 3506 up-regulated genes and 2855 down-regulated genes. Real-Time PCR of ten selected genes validated the RNA-Seq results as the correlation between them is 0.98. Functional and network analysis of Differentially Expressed Genes (DEGs) showed altered regulation of ElF2 signalling, mTOR signalling, proliferation of cells of the lymphoid system, signalling by Rho family GTPases and synaptogenesis signalling in spleen. We have also identified modified expression of IFIT5, PI3K, AGT and PLP1 genes in NDV-GVII infected chickens. Our findings in activation of autophagy-mediated cell death, lymphotropic and synaptogenesis signalling pathways provide new insights into the molecular pathogenesis of this newly emerged NDV-GVII.
Highlights
Analysis of the fusion protein gene of Newcastle disease virus (NDV) indicates that circulating strains in Indonesia are belonging to genotype VII.[1] with a mean death time (MDT) from 33 and 30 h as their pathogenicity index[9,11,12]
We aimed to identify the molecular basis of pathogenesis of newly emerged NDV-GVII using mRNA profiling of spleen tissues in experimentally infected chickens
To examine effects of virus on experimentally challenged birds, the Ross broiler Specific Pathogen Free (SPF) chickens were inoculated with a genotype VII NDV
Summary
Analysis of the fusion protein gene of NDVs indicates that circulating strains in Indonesia are belonging to genotype VII.[1] with a mean death time (MDT) from 33 and 30 h as their pathogenicity index[9,11,12]. Different studies have shown that infection with the virulent strains of NDV will increase the apoptosis in lymphoid tissue and immune cells[25,29,30,31]. The Mega strain used in our challenge experiment carries the RRQKRF motif sequence in the fusion protein, and has been reported as pathonenicity indicator of the NDV even in genetically modified lentogenic strains[40,41]. We have focused on cell death related pathways and functional analysis of genes to reveal their potential roles in massive cellular depletion in spleen lymphoid tissues. To our knowledge, this is the first in vivo study investigating gene expression profile of this velogenic strain
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