Six Hours after Infection, the Metabolic Changes Induced by WSSV Neutralize the Host's Oxidative Stress Defenses.
Levels of intracellular ROS (reactive oxygen species) were significantly increased in hemocytes collected from WSSV-infected shrimp within the first 30-120 min after infection. Measurement of the NADPH/NADP(+) and GSH/GSSG ratios revealed that after a significant imbalance toward the oxidized forms at 2 hpi, redox equilibrium was subsequently restored. Meanwhile, high levels of lactic acid production, elevated NADH/NAD(+) ratios, and metabolic changes in the glycolysis pathway show that the Warburg effect was triggered by the virus. The timing of these changes suggests that WSSV uses this metabolic shift into aerobic glycolysis to counteract the high levels of ROS produced in response to viral infection. We further show that if the Warburg effect is inhibited by chemical inhibition of the PI3K-Akt-mTOR signaling pathway, or if the pentose phosphate pathway is chemically inhibited, then in both cases, the production of intracellular ROS is sustained. We conclude that WSSV uses the PI3K-Akt-mTOR-regulated Warburg effect to restore host redox balance and to counter the ROS produced by the host in response to WSSV infection. We also found that pyruvate kinase activity was inhibited by WSSV. This inhibition is likely to increase the availability of the raw materials essential for WSSV gene expression and replication.
Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.|Department of Life Science, National Taiwan University, Taipei 106, Taiwan.
I-Tung
IT
Chen
Technology Commons, National Taiwan University, Taipei 106, Taiwan.|Department of Applied Chemistry, National Chiayi University, Chiayi 600, Taiwan.
Der-Yen
DY
Lee
Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
Yun-Tzu
YT
Huang
Department of Life Science, National Taiwan University, Taipei 106, Taiwan.
Guang-Hsiung
GH
Kou
Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
Han-Ching
HC
Wang
Graduate Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.|Center for Systems Biology, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 106, Taiwan.
Geen-Dong
GD
Chang
Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.|Department of Life Science, National Taiwan University, Taipei 106, Taiwan.
Chu-Fang
CF
Lo
D000818:Animals; D060829:Arthropod Proteins / Q000378:metabolism*; D006019:Glycolysis; D006434:Hemocytes / Q000378:metabolism*; D018384:Oxidative Stress; D033561:Penaeidae / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D010427:Pentose Phosphate Pathway; D011770:Pyruvate Kinase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D046848:White spot syndrome virus 1 / Q000502:physiology*
D060829:Arthropod Proteins; D017382:Reactive Oxygen Species; D011770:Pyruvate Kinase