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Differential Immune Transcriptome and Modulated Signalling Pathways in Rainbow Trout Infected with Viral Haemorrhagic Septicaemia Virus (VHSV) and Its Derivative Non-Virion (NV) Gene Deleted

机译:虹鳟感染病毒性败血病病毒(VHSV)及其衍生的非病毒体(NV)基因缺失的差异免疫转录组和调节的信号通路

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摘要

Viral haemorrhagic septicaemia virus (VHSV) is one of the worst viral threats to fish farming. Non-virion (NV) gene-deleted VHSV (dNV-VHSV) has been postulated as an attenuated virus, because the absence of the gene leads to lower induced pathogenicity. However, little is known about the immune responses driven by dNV-VHSV and the wild-type (wt)-VHSV in the context of infection. Here, we obtained the immune transcriptome profiling in trout infected with dNV-VHSV and wt-VHSV and the pathways involved in immune responses. As general results, dNV-VHSV upregulated more trout immune genes than wt-VHSV (65.6% vs 45.7%, respectively), whereas wt-VHSV maintained more non-regulated genes than dNV-VHSV (45.7% vs 14.6%, respectively). The modulated pathways analysis (Gene-Set Enrichment Analysis, GSEA) showed that, when compared to wt-VHSV infected trout, the dNV-VHSV infected trout upregulated signalling pathways ( = 19) such as RIG-I (retinoic acid-inducible gene-I) like receptor signalling, Toll-like receptor signalling, type II interferon signalling, and nuclear factor kappa B (NF-kappa B) signalling, among others. The results from individual genes and GSEA demonstrated that wt-VHSV impaired the activation at short stages of infection of pro-inflammatory, antiviral, proliferation, and apoptosis pathways, delaying innate humoral response and cellular crosstalk, whereas dNV-VHSV promoted the opposite effects. Therefore, these results might support future studies on using dNV-VHSV as a potential live vaccine.
机译:病毒性败血症病毒(VHSV)是对养鱼业最严重的病毒威胁之一。假定非病毒颗粒(NV)基因缺失的VHSV(dNV-VHSV)为减毒病毒,因为该基因的缺失会导致较低的致病性。但是,关于感染情况下由dNV-VHSV和野生型(wt)-VHSV驱动的免疫应答知之甚少。在这里,我们获得了感染了dNV-VHSV和wt-VHSV的鳟鱼的免疫转录组谱以及涉及免疫应答的途径。总体而言,dNV-VHSV上调的鳟鱼免疫基因多于wt-VHSV(分别为65.6%和45.7%),而wt-VHSV保持的非调控基因多于dNV-VHSV(分别为45.7%和14.6%)。调制途径分析(基因组富集分析,GSEA)显示,与wt-VHSV感染的鳟鱼相比,dNV-VHSV感染的鳟鱼上调了信号传导途径(= 19),例如RIG-I(视黄酸诱导基因- I)像受体信号转导,Toll样受体信号转导,II型干扰素信号转导和核因子κB(NF-κB)信号转导等。单个基因和GSEA的结果表明,wt-VHSV在促炎,抗病毒,增殖和凋亡途径感染的短期阶段损害了激活,延迟了先天的体液反应和细胞串扰,而dNV-VHSV促进了相反的作用。因此,这些结果可能支持将来使用dNV-VHSV作为潜在活疫苗的研究。

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