Multi-omics analysis of rainbow trout hepatocytes reveals the molecular mechanism of nano-selenium against IHNV

Infectious hematopoietic necrosis irus (IHNV) poses a significant threat to rainbow trout farming. While the antiviral effects of nano-selenium have been documented, its efficacy against IHNV and the underlying molecular mechanisms remain poorly understood. This study utilized rainbow trout hepatocytes as a model system. Cells were pre-incubated with 10 µg/mL nano-selenium for 24 h, then infected with IHNV and further incubated with nano-selenium for 72 h. Biochemical parameters, cell morphology, and apoptosis were measured at different time points following IHNV infection (3, 6, 12, 24, 36, 48, 60, and 72 hpi). Transcriptomic and metabolomic analyses were performed on representative samples collected at key time points. The results showed that IHNV infection induces oxidative stress in cells and significantly impairs their antioxidant capacity and immune function. Nano-selenium significantly inhibited IHNV replication, enhanced the levels of antioxidant- and immune-related indicators, maintained normal cell morphology, and suppressed apoptosis. Multi-omics analysis revealed that IHNV infection activates innate immune signaling pathways, while nano-selenium inhibits necroptosis in cells. Glycerophospholipid-related metabolites were altered during IHNV infection, suggesting that IHNV may affect cellular membrane homeostasis. Nano-selenium may help maintain membrane stability and promote the GSH-GSSG redox cycle through the glutathione metabolic pathway, thereby reducing cellular lipid peroxidation and inhibiting IHNV replication. This study provides the first evidence of the antiviral activity of nano-selenium against IHNV and, through multi-omics analysis, provides insights into its potential antiviral mechanisms at the cellular level, thereby offering a new theoretical basis for the development of nutritional antiviral strategies for rainbow trout.