Integrated profiling of global metabolomic and transcriptomic responses to viral hemorrhagic septicemia virus infection in olive flounder
Integrated profiling of global metabolomic and transcriptomic responses to viral hemorrhagic septicemia virus infection in olive flounder
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DOI：
10.1016/j.fsi.2017.10.007
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发表时间：
2017-12-01
影响因子：
4.7
通讯作者：
Hwang, Geum-Sook
中科院分区：
文献类型：
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作者：
Cho, Se-Young;Kwon, Yong -Kook;Hwang, Geum-Sook
病毒性出血性败血症病毒（VHSV）是危害养殖鱼类最严重的病毒病原之一。在这项研究中，我们测量了VHSV的复制在感染后9，24，72和120小时稳步增加，并在72 hpi观察到坏死的进展。我们使用Illumina HiSeq 2000和超高效液相色谱/四极杆飞行时间质谱对每个感染时间收集的肾脏组织进行转录组学和代谢组学分析，以研究VHSV感染橄榄比目鱼肾脏的机制。共选择了13，862个mRNA分子和72种代谢产物来鉴定感染机制，并使用KEGG途径数据库整合它们。6个KEGG代谢途径，包括碳水化合物代谢，氨基酸代谢，脂质代谢，运输和催化，代谢的辅因子和维生素，和能量代谢，显着抑制，而免疫系统被激活的VHSV感染。在VHSV感染后，观察到氨基酸如缬氨酸、亮氨酸和异亮氨酸以及它们的衍生物肉毒碱的水平降低。此外，还观察到花生四烯酸水平升高。利用KEGG通路数据库对转录组和代谢组进行综合分析，揭示了橄榄比目鱼肾脏对VHSV感染的四种反应。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被抑制。这是第一个描述橄榄比目鱼对VHSV感染的代谢反应机制的研究。结果表明，抑制ATP合成和抗氧化系统，如谷胱甘肽和过氧化物酶体信号，可能是坏死的原因，而免疫系统的激活可能导致VHSV感染的橄榄比目鱼肾组织的炎症。
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.