Chloroquine inhibits Spring viremia of carp virus replication by modulating autophagy and metabolic pathways.

Spring viremia of carp virus (SVCV) severely threatens cyprinid aquaculture, yet the role of autophagy in SVCV infection remains unclear. Here, SVCV infection was associated with enhanced autophagic activity and autophagic flux in common carp and EPC cells. Pharmacological perturbation of autophagy revealed that rapamycin treatment increased SVCV gene expression and aggravated SVCV-induced cytopathic effects, whereas chloroquine blocked autophagic flux, suppressed viral gene expression, and mitigated virus-induced cellular damage. Transcriptomic analysis identified 1,868 differentially expressed genes after chloroquine treatment, with major changes in lysosome/autophagy-related pathways, glycan degradation, ion transport, cell cycle, DNA replication, and DNA repair. Metabolomic and integrated multi-omics analyses revealed changes in amino sugar and nucleotide sugar metabolism, steroid biosynthesis, riboflavin metabolism, and amino acid metabolism. Functional validation showed that diflorasone and all-trans-retinal reduced SVCV-G expression, alleviated cytopathic effects, and improved survival after SVCV infection. These findings suggest that SVCV infection is associated with enhanced autophagic flux, whereas chloroquine treatment blocks autophagic flux and is accompanied by reduced SVCV gene expression.