دورية أكاديمية
Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid.
العنوان: | Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid. |
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المؤلفون: | Liu L; College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 510642, China., Zhang Y; College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 510642, China.; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, Guangdong 511464, China., Yuan MD; College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 510642, China., Xiao DM; College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 510642, China., Xu WH; College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 510642, China., Zheng Q; College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 510642, China., Qin QW; College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 510642, China.; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, Guangdong 511464, China.; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, Guangdong 519082, China. E-mail: qinqw@scau.edu.cn., Huang YH; College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 510642, China.; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, Guangdong 511464, China. E-mail: huangyh@scau.edu.cn., Huang XH; College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 510642, China.; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, Guangdong 511464, China. E-mail: huangxh@scau.edu.cn. |
المصدر: | Zoological research [Zool Res] 2024 May 18; Vol. 45 (3), pp. 520-534. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Science Press Country of Publication: China NLM ID: 101697192 Publication Model: Print Cited Medium: Internet ISSN: 2095-8137 (Print) Linking ISSN: 20958137 NLM ISO Abbreviation: Zool Res Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Beijing, China : Science Press, 2016- |
مواضيع طبية MeSH: | alpha-Linolenic Acid*/metabolism , Fish Diseases*/virology , Fish Diseases*/metabolism , Liver*/metabolism , Liver*/virology , Iridovirus*/physiology, Animals ; DNA Virus Infections/veterinary ; DNA Virus Infections/virology ; Metabolomics ; Antiviral Agents/pharmacology ; Transcriptome ; Metabolic Reprogramming ; Multiomics |
مستخلص: | Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate; however, the molecular mechanisms underpinning its pathogenesis are not well elucidated. Here, a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus (SGIV), focusing on the roles of key metabolites. Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver. Furthermore, SGIV significantly reduced the contents of lipid droplets, triglycerides, cholesterol, and lipoproteins. Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways, with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid (ALA), consistent with disturbed lipid homeostasis in the liver. Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide, carbohydrate, amino acid, and lipid metabolism, supporting the conclusion that SGIV infection induced liver metabolic reprogramming. Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade. Of note, integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid (LA) metabolites, and the accumulation of L-glutamic acid (GA), accompanied by alterations in immune, inflammation, and cell death-related genes. Further experimental data showed that ALA, but not GA, suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host. Collectively, these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases. |
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فهرسة مساهمة: | Keywords: Alpha-linolenic acid; Anti-inflammatory; Iridovirus; Liver damage; Metabolic reprogramming; SGIV Local Abstract: [Publisher, Chinese] 虹彩病毒病因其高死亡率已成为全球水产养殖业的一大威胁,但其发病机制尚不明确。该研究对新加坡石斑鱼虹彩病毒(Singapore grouper iridovirus,SGIV)感染的石斑鱼肝脏进行多组学分析,并探究其关键代谢物的抗病毒功能。病理和生化分析表明:SGIV感染可引起石斑鱼肝脏明显的组织病理损伤及谷丙转氨酶、谷草转氨酶、酸性磷酸酶、碱性磷酸酶及乳酸脱氢酶活性的变化。同时,SGIV感染显著降低了鱼体肝脏脂滴、甘油三酯、胆固醇和脂蛋白的含量。代谢组学分析显示222个差异代谢物显著富集在19条通路,其中甘油磷酸酯、α -亚麻酸(alpha-linolenic acid,ALA)、亚油酸(linoleic acid,LA)等脂质代谢物丰度显著下调。转录组学和代谢组学联合分析表明SGIV感染诱导了肝脏代谢重编程,且差异代谢物和差异表达基因共同富集在细胞生长与死亡信号及核苷酸、碳水化合物、氨基酸和脂质代谢相关通路。转录组学和蛋白质组学联合分析显示,SGIV感染激活了吞噬体-免疫抑制-代谢失调-坏死信号级联中的关键分子事件。进一步对转录组、蛋白质组和代谢组关联分析表明,差异代谢物L -谷氨酸(L-glutamic acid,GA)、ALA和 LA丰度的变化与免疫、炎症和细胞死亡相关基因或蛋白表达水平的改变密切相关。此外,体外实验表明ALA添加可通过激活宿主抗氧化及抗炎作用抑制SGIV复制。综上,该研究结果首次全面揭示了鱼类虹彩病毒感染后宿主反应动力学特征,并揭示ALA在虹彩病毒疾病预防和治疗中的潜在作用。. |
سلسلة جزيئية: | BioProject PRJNA804746 |
المشرفين على المادة: | 0RBV727H71 (alpha-Linolenic Acid) 0 (Antiviral Agents) |
تواريخ الأحداث: | Date Created: 20240429 Date Completed: 20240429 Latest Revision: 20240731 |
رمز التحديث: | 20240801 |
مُعرف محوري في PubMed: | PMC11188608 |
DOI: | 10.24272/j.issn.2095-8137.2024.028 |
PMID: | 38682434 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2095-8137 |
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DOI: | 10.24272/j.issn.2095-8137.2024.028 |