Chinchilla Blanca, Encinas Paloma, Coll Julio M, Gomez-Casado Eduardo
Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, MA 02114, USA.
Department of Biotechnology, National Agricultural and Food Research and Technology Institute (INIA), 28040 Madrid, Spain.
Vaccines (Basel). 2020 Jan 30;8(1):58. doi: 10.3390/vaccines8010058.
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.
病毒性出血性败血症病毒（VHSV）是鱼类养殖面临的最严重病毒威胁之一。非病毒粒子（NV）基因缺失的VHSV（dNV-VHSV）被假定为一种减毒病毒，因为该基因的缺失导致诱导致病性降低。然而，在感染情况下，关于dNV-VHSV和野生型（wt）-VHSV驱动的免疫反应知之甚少。在这里，我们获得了感染dNV-VHSV和wt-VHSV的鳟鱼的免疫转录组图谱以及免疫反应所涉及的途径。总体结果显示，与wt-VHSV相比，dNV-VHSV上调的鳟鱼免疫基因更多（分别为65.6%和45.7%），而wt-VHSV维持的未调节基因比dNV-VHSV更多（分别为45.7%和14.6%）。调节通路分析（基因集富集分析，GSEA）表明，与感染wt-VHSV的鳟鱼相比，感染dNV-VHSV的鳟鱼上调了信号通路（ = 19），如视黄酸诱导基因I（RIG-I）样受体信号通路、Toll样受体信号通路、II型干扰素信号通路和核因子κB（NF-κB）信号通路等。单个基因和GSEA的结果表明，wt-VHSV在感染的短阶段损害了促炎、抗病毒、增殖和凋亡通路的激活，延迟了先天性体液反应和细胞间相互作用，而dNV-VHSV则产生相反的效果。因此，这些结果可能为未来将dNV-VHSV用作潜在活疫苗的研究提供支持。
