Replication of the shrimp virus WSSV depends on glutamate-driven anaplerosis

Chun Yuan Li, Yi Jan Wang, Shiao Wei Huang, Cheng Shun Cheng, Han Ching Wang

研究成果: Article同行評審

30 引文 斯高帕斯(Scopus)

摘要

Infection with the white spot syndrome virus (WSSV) induces a metabolic shift in shrimp that resembles the "Warburg effect" in mammalian cells. This effect is triggered via activation of the PI3K-Akt-mTOR pathway, and it is usually accompanied by the activation of other metabolic pathways that provide energy and direct the flow of carbon and nitrogen. Here we show that unlike the glutamine metabolism (glutaminolysis) seen in most cancer cells to double deaminate glutamine to produce glutamate and the TCA cycle intermediate α-ketoglutarate (α-KG), at the WSSV genome replication stage (12 hpi), although glutaminase (GLS) expression was upregulated, only glutamate was taken up by the hemocytes of WSSV-infected shrimp. At the same time, we observed an increase in the activity of the two enzymes that convert glutamate to α-KG, glutamate dehydrogenase (GDH) and aspartate aminotransferase (ASAT). α-ketoglutarate concentration was also increased. A series of inhibition experiments suggested that the up-regulation of GDH is regulated by mTORC2, and that the PI3K-mTORC1 pathway is not involved. Suppression of GDH and ASAT by dsRNA silencing showed that both of these enzymes are important for WSSV replication. In GDH-silenced shrimp, direct replenishment of α-KG rescued both ATP production and WSSV replication. From these results, we propose a model of glutamate-driven anaplerosis that fuels the TCA cycle via α-KG and ultimately supports WSSV replication.

原文English
文章編號e0146902
期刊PloS one
11
發行號1
DOIs
出版狀態Published - 2016 1月 11

All Science Journal Classification (ASJC) codes

  • 一般生物化學,遺傳學和分子生物學
  • 一般農業與生物科學
  • 多學科

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