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

Iridovirus has become a great threat to global aquaculture due to its high mortality, while the molecular events in virus pathogenesis are not well elucidated. Here, the multi-omics approach was performed with Singapore grouper iridovirus (SGIV)-infected groupers, and the roles of key metabolites were investigated. SGIV induced obvious histopathological damage and changes of metabolic enzymes in liver. Besides, SGIV significantly decreased the contents of lipid droplets, triglycerides, cholesterol, and lipoprotein. Metabolome analysis showed that that the differentially metabolites were enriched in 19 pathways, and lipid metabolites, including glycerophosphates and alpha-linolenic acid (ALA) were down-regulated, which is consistent with the disturbed lipid homeostasis in liver. Combining with transcriptomic and metabolomic data, the top enriched pathways were related to cell growth and death, nucleotide, carbohydrate, amino acid, and lipid metabolisms, supporting the conclusion that SGIV infection induced liver metabolic reprogramming. Integrative transcriptomic and proteomic analysis indicated that SGIV infection activated the crucial molecular events in phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade. Of note, integrative multi-omics analysis demonstrated that metabolites ALA and linoleic acid (LA) were consumed, while L-glutamic acid (GA) was accumulated, accompanied by the alteration of immune, inflammation, and cell death related genes. Further experimental data showed that ALA, but not GA suppressed SGIV replication by activating host antioxidant and anti-inflammatory effects. Together, our findings for the first time provide a comprehensive resource to understand the landscape of host response dynamics during fish iridovirus infection, and highlight the antiviral roles of ALA in the prevention and treatment for iridovirus diseases.