Huang Youhua, Zhang Ya, Zheng Jiaying, Wang Liqun, Qin Qiwei, Huang Xiaohong
Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, China.
Lingnan Guangdong Laboratory of Modern Agriculture, Guangzhou, China.
Cell Microbiol. 2020 Sep;22(9):e13216. doi: 10.1111/cmi.13216. Epub 2020 Jun 4.
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.
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重大经济损失。然而，RGNNV感染期间宿主细胞代谢的变化仍 largely 未知。在此，研究了RGNNV感染期间的全球代谢谱以及细胞脂肪酸合成在RGNNV感染中的作用。随着感染的进展，与 mock 感染细胞相比，RGNNV感染细胞中有71种细胞内代谢物发生了显著变化。参与氨基酸生物合成和代谢的代谢物水平显著降低，而与脂肪酸合成相关的代谢物水平在RGNNV感染期间显著上调。其中，色氨酸和油酸被评估为RGNNV感染的最关键生物标志物。此外，RGNNV感染诱导了脂滴的形成和脂肪酸合酶（FASN）的重新定位，表明RGNNV诱导并需要脂肪生成来进行病毒感染。外源性添加棕榈酸（PA）增强了RGNNV感染，抑制FASN和乙酰辅酶A羧化酶（ACC）显著降低了RGNNV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氧化也显著降低了病毒复制。这些数据表明，细胞脂肪酸合成和线粒体β氧化对于RGNNV完成病毒生命周期至关重要。因此，首次证明体外RGNNV感染改变了宿主细胞代谢，在此过程中，细胞脂肪酸合成是RGNNV复制的重要组成部分。
