The 2-aminoadipic acid (2-AAA) regulates grass carp ULK2 to inhibit GCRV replication

Grass carp is an important commercial fish in China that is plagued by various diseases, especially the hemorrhagic disease induced by grass carp reovirus (GCRV). Autophagy, a highly conserved biological process among eukaryotes, is pivotal in maintaining cellular homeostasis and managing various stressors, including viral infections. Uncoordinated (Unc) 51-like kinase 2 (ULK2) is considered an initiator of the autophagic process. In this study, we successfully cloned and isolated the ULK2 gene from grass carp. We observed that its expression levels were markedly altered following exposure to GCRV or pathogen-associated molecular patterns (PAMPs). Overexpression of CiULK2 in grass carp ovary cells (GCO) promoted GCRV replication. Conversely, CiULK2 knockdown resulted in inhibited viral loads compared to the control group. Moreover, we also reveal that 2-aminoadipic acid (2-AAA), a representative autophagy related metabolite, can inhibit autophagy and viral replication. Notably, these roles of CiULK2 in autophagy and GCRV replication were reversed upon treatment with the 2-AAA. Collectively, our findings demonstrate the 2-AAA regulates CiULK2 to inhibit GCRV replication.