School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, Australia.
The Davies Research Centre, School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, Australia.
Sci Rep. 2021 Sep 2;11(1):17570. doi: 10.1038/s41598-021-96929-w.
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.
新城疫病毒（NDV）近年来在东南亚，特别是印度尼西亚引起了重大疫情爆发。最近出现的基因型 VII NDV（NDV-GVII）已经将其嗜性从胃肠/呼吸道嗜性转变为淋巴嗜性病毒，侵犯包括脾脏和法氏囊在内的淋巴器官，导致严重的淋巴耗竭。在这项研究中，我们旨在鉴定导致这种强毒 NDV-GVII 引起的疾病的候选基因和生物学途径。我们对感染 NDV-GVII 和对照组的鸡进行了基于 RNA-Seq 的脾脏转录组分析。总共检测到 6361 个差异表达的基因，包括 3506 个上调基因和 2855 个下调基因。十个选定基因的实时 PCR 验证了 RNA-Seq 结果，因为它们之间的相关性为 0.98。差异表达基因（DEGs）的功能和网络分析表明，ElF2 信号、mTOR 信号、淋巴系统细胞增殖、Rho 家族 GTPase 信号和突触发生信号的调节发生改变。我们还发现感染 NDV-GVII 的鸡中 IFIT5、PI3K、AGT 和 PLP1 基因的表达发生改变。我们对自噬介导的细胞死亡、淋巴嗜性和突触发生信号通路的激活的发现，为这种新出现的 NDV-GVII 的分子发病机制提供了新的见解。
