Oncotarget

Research Papers:

Glutamine and glutaminolysis are required for efficient replication of infectious spleen and kidney necrosis virus in Chinese perch brain cells

Xiaozhe Fu, Xianqin Hu, Ningqiu Li, Feifei Zheng, Xingxing Dong, Jing Duan, Qiang Lin, Jiagang Tu, Lijuan Zhao, Zhibin Huang, Jianguo Su and Li Lin _

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Oncotarget. 2017; 8:2400-2412. https://doi.org/10.18632/oncotarget.13681

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Abstract

Xiaozhe Fu1,2,4,*, Xianqin Hu2,3,*, Ningqiu Li1,2, Feifei Zheng2, Xingxing Dong2, Jing Duan2, Qiang Lin1,2, Jiagang Tu2, Lijuan Zhao2, Zhibin Huang1, Jianguo Su2,4, Li Lin2,5

1Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture, Key Laboratory of Aquatic Animal Immune Technology, Guangdong Provinces, Guangzhou, Guangdong, 510380, China

2Department of Aquatic Animal Medicine, Research Center of Marine Biology, College of Fisheries, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province Huazhong Agricultural University, Wuhan, Hubei, 430070, China

3School of Animal Sciences and Nutritional Engineering, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China

4College of Animal Science and Technology, Northwest A and F University, Shanxi Key Laboratory of Molecular Biology for Aquaculture, Yangling, 712100, China

5State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan Provincial Key Laboratory for Tropical Hydrobiology and Biotechnology, College of Marine Science, Hainan University, Haikou 570228, China

*These authors contributed equally to the work

Correspondence to:

Li Lin, email: [email protected]

Ningqiu Li, email: [email protected]

Keywords: Siniperca chuatsi, ISKNV, glutamine, glutaminolysis, TCA cycle

Received: April 24, 2016     Accepted: November 21, 2016     Published: November 29, 2016

ABSTRACT

Viruses rely on host cellular metabolism for energy and macromolecule synthesis during their replication. Infectious spleen and kidney necrosis virus (ISKNV) causes significant economic losses in the Chinese perch (Siniperca chuatsi) industry worldwide. However, little is known about the relationship between ISKNV replication and cellular metabolism. Using transcriptomic analysis, we observed that glutamine metabolism in Chinese perch brain (CPB) cells is altered during ISKNV infection. Moreover, ISKNV replication was decreased in CPB cells cultured in the glutamine-depleted medium. ISKNV replication was also inhibited in CPB cells cultured in the presence of bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (an inhibitor of glutaminase), (–)-epigallocatechinmo nogallate (an inhibitor of glutamate dehydrogenase) or L-buthionine sulfoximine (an inhibitor of glutathione synthesis). However, virus replication was rescued by the addition of multiple tricarboxylic acid cycle intermediates, ATP, or glutathione reduced ethyl ester. ATP and reduced glutathione/oxidized glutathione levels were increased in CPB cells infected with ISKNV, but were decreased in CPB cells cultured in glutamine-depleted medium. These results indicate ISKNV infection induces glutaminolysis to accommodate the biosynthetic and energy needs for its efficient virus replication.


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