Biological Disaster Analysis Team, Korea Basic Science Institute, Daejeon 169-148, Republic of Korea.
Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, Republic of Korea.
Fish Shellfish Immunol. 2017 Dec;71:220-229. doi: 10.1016/j.fsi.2017.10.007. Epub 2017 Oct 7.
Viral hemorrhagic septicemia virus (VHSV) is one of the most serious viral pathogen that infects farmed fish. In this study, we measured the replication of VHSV increased steadily at 9, 24, 72, and 120 h after infection and progression of necrosis was observed at 72 hpi. We performed transcriptomic and metabolomics profiling of kidney tissues collected at each infection time using Illumina HiSeq2000 and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectroscopy to investigate the mechanisms of VHSV infection in the kidneys of olive flounder. A total of 13,862 mRNA molecules and 72 metabolites were selected to identify the mechanisms of infection and they were integrated using KEGG pathway database. Six KEGG metabolic pathways, including carbohydrate metabolism, amino acid metabolism, lipid metabolism, transport and catabolism, metabolism of cofactors and vitamins, and energy metabolism, were significantly suppressed, whereas the immune system was activated by VHSV infection. A decrease in levels of amino acids such as valine, leucine, and isoleucine, as well as in their derivative carnitines, was observed after VHSV infection. In addition, an increase in arachidonic acid level was noted. Integrated analysis of transcriptome and metabolome using KEGG pathway database revealed four types of responses in the kidneys of olive flounder to VHSV infection. Among these, the mechanisms related to the immune system and protein synthesis were activated, whereas ATP synthesis and the antioxidant system activity were suppressed. This is the first study describing the mechanisms of metabolic responses to VHSV infection in olive flounder. The results suggest that the suppression of ATP synthesis and antioxidant systems, such as glutathione and peroxisome signaling, could be the cause of necrosis, whereas the activation of the immune system could result in the inflammation of kidney tissue in VHSV-infected olive flounder.
病毒性出血性败血症病毒 (VHSV) 是感染养殖鱼类的最严重的病毒病原体之一。在本研究中，我们测量到 VHSV 的复制在感染后 9、24、72 和 120 小时稳步增加，并且在 72 hpi 时观察到坏死的进展。我们使用 Illumina HiSeq2000 和超高效液相色谱/四极杆飞行时间质谱对在每个感染时间收集的肾脏组织进行转录组和代谢组学分析，以研究 VHSV 在橄榄石斑鱼肾脏中的感染机制。共选择了 13862 个 mRNA 分子和 72 种代谢物来鉴定感染机制，并使用 KEGG 途径数据库对其进行整合。包括碳水化合物代谢、氨基酸代谢、脂质代谢、运输和分解代谢、辅助因子和维生素代谢以及能量代谢在内的六个 KEGG 代谢途径显著受到抑制，而免疫系统则被 VHSV 感染激活。VHSV 感染后，观察到缬氨酸、亮氨酸和异亮氨酸等氨基酸及其衍生的肉碱水平下降。此外，还注意到花生四烯酸水平增加。使用 KEGG 途径数据库对转录组和代谢组进行综合分析，揭示了橄榄石斑鱼肾脏对 VHSV 感染的四种反应类型。其中，与免疫系统和蛋白质合成相关的机制被激活，而 ATP 合成和抗氧化系统活性受到抑制。这是首次描述橄榄石斑鱼对 VHSV 感染的代谢反应机制的研究。结果表明，ATP 合成和抗氧化系统（如谷胱甘肽和过氧化物酶体信号）的抑制可能是坏死的原因，而免疫系统的激活可能导致 VHSV 感染的肾脏组织炎症。
