PLoS pathogens, 2014-06, Vol.10 (6), p.e1004196-e1004196
2014
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- Autor(en) / Beteiligte
- Titel
- An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway
- Ist Teil von
- PLoS pathogens, 2014-06, Vol.10 (6), p.e1004196-e1004196
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7374, 1553-7366eISSN: 1553-7374DOI: 10.1371/journal.ppat.1004196Titel-ID: cdi_plos_journals_1547572847
- Format
- –
- Schlagworte
- 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