| 描述信息 |
Viral nervous necrosis (VNN) disease, which caused by fish nodavirus, is one of the most typical viral disease with high contagious and high mortality in marine fish. Our previous study showed that RGNNV induced and exploited cellular fatty acid synthesis for virus infection. However, roles of lipid metabolism during RGNNV infection still remained largely uncertain. Here, the global lipidomic profiles of RGNNV in infected grouper cells were analyzed by UPLC-QE-Orbitrap-MS/MS, and the crucial roles of ceramide during RGNNV infection were investigated. RGNNV infection significantly altered lipid homeostasis in vitro, evidence by an increase in the levels of sphingolipids (SPs). Of note, almost all detected ceramides displayed elevated abundance in RGNNV-infected cells, suggesting that SPs might play important roles in RGNNV infection. Consistently, the mRNA expression of 5 genes related to ceramide synthesis were significantly upregulated upon RGNNV infection. Moreover, a significant increase of ceramide accumulation, which was co-localized with CP protein, was observed in RGNNV infected grouper cells, further confirming the participant of ceramide in RGNNV replication. Besides, ectopic expression of RGNNV coat protein (CP) also altered the content of the host lipid metabolites, especially increased the levels of ceramide species. Inhibition of ceramide synthesis significantly suppressed RGNNV replication in vitro. Moreover, the addition of exogenous C16-ceramide (d18:1/16:0) prior to infection significantly increased RGNNV replication via promoting the expression of RGNNV-induced autophagy related genes and proinflammatory factors. Taken together, these data indicated that RGNNV infection induced sphingolipid metabolisms and ceramide flux was a key mediator for RGNNV infection. |
