Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid  

作　　者：Lin Liu Ya Zhang Meng-Di Yuan Dong-Miao Xiao Wei-Hua Xu Qi Zheng Qi-Wei Qin You-Hua Huang Xiao-Hong Huang 

机构地区：[1]College of Marine Sciences,South China Agricultural University,Guangdong Laboratory for Lingnan Modern Agriculture,Guangzhou,Guangdong 510642,China [2]Nansha-South China Agricultural University Fishery Research Institute,Guangzhou,Guangdong 511464,China [3]Southern Marine Science and Engineering Guangdong Laboratory,Zhuhai,Guangdong 519082,China

出　　处：《Zoological Research》2024年第3期520-534,共15页动物学研究（英文）

基　　金：supported by the National Natural Science Foundation of China(31930115,32173007);China Agriculture Research System of MOF and MARA(CARS-47-G16);Basic and Applied Basic Research Foundation of Guangdong Province(2022A1515010595)。

摘　　要：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.

关 键 词：IRIDOVIRUS Liver damage Metabolic reprogramming SGIV Alpha-linolenic acid ANTIINFLAMMATORY 

分 类 号：S941.41[农业科学—水产养殖]