White spot syndrome virus infection promotes the PI3K-Akt-mTOR pathway-regulated Warburg effect to reduce oxidative stress in Penaeus vannamei

• Main Authors: I-Tung Chen, 陳顗同
• Other Authors: 羅竹芳
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/05178563997871402214

博士 === 國立臺灣大學 === 生命科學系 === 103 === Here we investigate how white spot syndrome virus (WSSV) alters its host’s metabolism to restore host redox balance and counter the immediate increase in ROS production that occurs after WSSV infection. Intracellular ROS levels were significantly increased in hemocytes collected from WSSV-infected shrimp within the first 30 min ~ 2 h post infection. Measurement of the NADPH/NADP+ and GSH/GSSG ratios revealed that after a significant initial imbalance toward the oxidized forms at 2 hpi, redox equilibrium was subsequently restored. Together with high levels of lactic acid production and an elevated NADH/NAD+ ratio, these changes suggest that WSSV induces aerobic glycolysis to counteract the high levels of ROS production that were triggered in response to viral infection. Suppression of the virus-induced Warburg effect by chemical inhibitor of PI3K-Akt-mTOR singling pathway cause the sustained production in intracellular ROS. A metabolomics analysis confirmed that glycolysis activity in shrimp was up-regulated after WSSV infection. However, pyruvate kinase activity was inhibited by WSSV, and accumulation of upstream metabolites caused glucose metabolism to be redirected into the pentose phosphate pathway and the serine and glycine biosynthesis pathway. Here we show that the initially high levels of ROS trigger by WSSV is combated by PI3k-Akt-mTOR regulated Warburg effect. Changes induced by WSSV infection cause re-routing of the host’s glycolytic metabolism into subsidiary pathways and increases the availability of raw materials that are essential for WSSV gene expression and replication.