An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway

In this study, we used a systems biology approach to investigate changes in the proteome and metabolome of shrimp hemocytes infected by the invertebrate virus WSSV (white spot syndrome virus) at the viral genome replication stage (12 hpi) and the late stage (24 hpi). At 12 hpi, but not at 24 hpi, th...

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Bibliographic Details
Published in:	PLoS pathogens 2014-06, Vol.10 (6), p.e1004196-e1004196
Main Authors:	Su, Mei-An, Huang, Yun-Tzu, Chen, I-Tung, Lee, Der-Yen, Hsieh, Yun-Chieh, Li, Chun-Yuan, Ng, Tze Hann, Liang, Suh-Yuen, Lin, Shu-Yu, Huang, Shiao-Wei, Chiang, Yi-An, Yu, Hon-Tsen, Khoo, Kay-Hooi, Chang, Geen-Dong, Lo, Chu-Fang, Wang, Han-Ching
Format:	Article
Language:	eng
Subjects:	Amino Acids - biosynthesis Amino Acids - metabolism Animals Biology Biology and Life Sciences Biosynthesis Cancer Citric Acid Cycle - genetics Colleges & universities Deoxyribonucleic acid Diseases DNA Energy Metabolism - genetics Gene expression Genomes Glucose metabolism Glycolysis - genetics Mass spectrometry Mechanistic Target of Rapamycin Complex 1 Mechanistic Target of Rapamycin Complex 2 Metabolites Metabolome - genetics Monomeric GTP-Binding Proteins - genetics Monosaccharides Multiprotein Complexes - antagonists & inhibitors Multiprotein Complexes - genetics Naphthyridines - pharmacology Penaeidae - metabolism Penaeidae - virology Pentose Phosphate Pathway - genetics Phosphatidylinositol 3-Kinases - metabolism Phosphorylation Physiological aspects Proteins Proteome - genetics Proteomics Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - metabolism Shrimps Sugars TOR Serine-Threonine Kinases - antagonists & inhibitors TOR Serine-Threonine Kinases - genetics TOR Serine-Threonine Kinases - metabolism Virus Replication - genetics White spot syndrome virus 1 - genetics White spot syndrome virus 1 - metabolism
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Summary:	In this study, we used a systems biology approach to investigate changes in the proteome and metabolome of shrimp hemocytes infected by the invertebrate virus WSSV (white spot syndrome virus) at the viral genome replication stage (12 hpi) and the late stage (24 hpi). At 12 hpi, but not at 24 hpi, there was significant up-regulation of the markers of several metabolic pathways associated with the vertebrate Warburg effect (or aerobic glycolysis), including glycolysis, the pentose phosphate pathway, nucleotide biosynthesis, glutaminolysis and amino acid biosynthesis. We show that the PI3K-Akt-mTOR pathway was of central importance in triggering this WSSV-induced Warburg effect. Although dsRNA silencing of the mTORC1 activator Rheb had only a relatively minor impact on WSSV replication, in vivo chemical inhibition of Akt, mTORC1 and mTORC2 suppressed the WSSV-induced Warburg effect and reduced both WSSV gene expression and viral genome replication. When the Warburg effect was suppressed by pretreatment with the mTOR inhibitor Torin 1, even the subsequent up-regulation of the TCA cycle was insufficient to satisfy the virus's requirements for energy and macromolecular precursors. The WSSV-induced Warburg effect therefore appears to be essential for successful viral replication.
ISSN:	1553-7374 1553-7366 1553-7374