Dual Regulation of Lipid Metabolism and Mitochondrial Respiratory Chain: The roles of Ec-GRIM19 during RGNNV Infection in orange-spotted grouper (Epinephelus coioides).

Gene associated with retinoid-interferon-induced mortality 19 (GRIM19) can affect viral infection by regulating lipid metabolism, and modulate inflammatory factors via the mitochondrial respiratory chain. However, the function of fish GRIM19s remains unclear. In this study, the GRIM19 gene (Ec-GRIM19) was identified from orange-spotted grouper (Epinephelus coioides). The amino acid sequence of Ec-GRIM19 shared highest identities with Epinephelus lanceolatus GRIM19. The in vivo analysis indicated that Ec-GRIM19 has the highest expression levels in the liver and kidney. The expression of Ec-GRIM19 was significantly down-regulated in GS cells after Red-spotted Grouper Nervous Necrosis Virus (RGNNV) infection. In vitro, overexpression of Ec-GRIM19 downregulated the expressions of lipid metabolism-related genes (SREBP1, FASN) and Capsid Protein (CP) and RNA-dependent RNA polymerase (RdRp) gene of RGNNV, induced the expressions of interferon-related factors (NLRP3, IL-1β and IL-18). And the knockdown of Ec-GRIM19 in vitro have the opposite regulatory effects. Besides, the production of ATP was suppressed, and the ROS level was increased, and the mitochondrial membrane potential was decreased, indicating inhibition of the mitochondrial respiratory chain. These data provide new insights to further investigate the interaction between fish and viral infections.