Red‐spotted grouper nervous necrosis virus (RGNNV), the causative agent of viral nervous necrosis disease, has caused high mortality and heavy economic losses in marine aquaculture worldwide. However, changes in host cell metabolism during RGNNV infection remain largely unknown. Here, the global metabolic profiling during RGNNV infection and the roles of cellular fatty acid synthesis in RGNNV infection were investigated. As the infection progressed, 71 intracellular metabolites were significantly altered in RGNNV‐infected cells compared with mock‐infected cells. The levels of metabolites involved in amino acid biosynthesis and metabolism were significantly decreased, whereas those that correlated with fatty acid synthesis were significantly up‐regulated during RGNNV infection. Among them, tryptophan and oleic acid were assessed as the most crucial biomarkers for RGNNV infection. In addition, RGNNV infection induced the formation of lipid droplets and re‐localization of fatty acid synthase (FASN), indicating that RGNNV induced and required lipogenesis for viral infection. The exogenous addition of palmitic acid (PA) enhanced RGNNV infection, and the inhibition of FASN and acetyl‐CoA carboxylase (ACC) significantly decreased RGNNV replication. Additionally, not only inhibition of palmitoylation and phospholipid synthesis, but also destruction of fatty acid β ‐oxidation significantly decreased viral replication. These data suggest that cellular fatty acid synthesis and mitochondrial β ‐oxidation are essential for RGNNV to complete the viral life cycle. Thus, it has been demonstrated for the first time that RGNNV infection in vitro overtook host cell metabolism and, in that process, cellular fatty acid synthesis was an essential component for RGNNV replication.

中文翻译：

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体外鱼类诺达病毒感染的代谢特征：RGNNV 诱导和利用细胞脂肪酸合成来感染病毒。

红斑石斑鱼神经坏死病毒（RGNNV）是病毒性神经坏死病的病原体，已在全球海水养殖中造成高死亡率和沉重的经济损失。然而，RGNNV 感染期间宿主细胞代谢的变化在很大程度上仍然未知。在这里，研究了 RGNNV 感染期间的整体代谢谱和细胞脂肪酸合成在 RGNNV 感染中的作用。随着感染的进展，与模拟感染细胞相比，RGNNV 感染细胞中的 71 种细胞内代谢物发生了显着变化。在 RGNNV 感染期间，参与氨基酸生物合成和代谢的代谢物水平显着降低，而与脂肪酸合成相关的代谢物水平显着上调。其中，色氨酸和油酸被评估为 RGNNV 感染最重要的生物标志物。此外，RGNNV 感染诱导脂滴的形成和脂肪酸合酶 (FASN) 的重新定位，表明 RGNNV 诱导并需要病毒感染的脂肪生成。外源性添加棕榈酸（PA）增强了 RGNNV 感染，FASN 和乙酰辅酶 A 羧化酶（ACC）的抑制显着降低了 RGNNV 的复制。此外，不仅抑制棕榈酰化和磷脂合成，而且破坏脂肪酸 外源性添加棕榈酸（PA）增强了 RGNNV 感染，FASN 和乙酰辅酶 A 羧化酶（ACC）的抑制显着降低了 RGNNV 的复制。此外，不仅抑制棕榈酰化和磷脂合成，而且破坏脂肪酸 外源性添加棕榈酸（PA）增强了 RGNNV 感染，FASN 和乙酰辅酶 A 羧化酶（ACC）的抑制显着降低了 RGNNV 的复制。此外，不仅抑制棕榈酰化和磷脂合成，而且破坏脂肪酸β-氧化显着减少病毒复制。这些数据表明细胞脂肪酸合成和线粒体β-氧化对于 RGNNV 完成病毒生命周期是必不可少的。因此，首次证明体外 RGNNV 感染超过了宿主细胞代谢，在该过程中，细胞脂肪酸合成是 RGNNV 复制的重要组成部分。