Research abstract
Article abstract
Nature Biotechnology 26, 1179 - 1186 (2008)
Published online: 28 September 2008 | doi:10.1038/nbt.1500
Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy
Joshua Munger1,2,5, Bryson D Bennett3,5, Anuraag Parikh3, Xiao-Jiang Feng4, Jessica McArdle2, Herschel A Rabitz4, Thomas Shenk1 & Joshua D Rabinowitz3
Abstract
Viruses rely on the metabolic network of their cellular hosts to provide energy and building blocks for viral replication. We developed a flux measurement approach based on liquid chromatography–tandem mass spectrometry to quantify changes in metabolic activity induced by human cytomegalovirus (HCMV). This approach reliably elucidated fluxes in cultured mammalian cells by monitoring metabolome labeling kinetics after feeding cells 13C-labeled forms of glucose and glutamine. Infection with HCMV markedly upregulated flux through much of the central carbon metabolism, including glycolysis. Particularly notable increases occurred in flux through the tricarboxylic acid cycle and its efflux to the fatty acid biosynthesis pathway. Pharmacological inhibition of fatty acid biosynthesis suppressed the replication of both HCMV and influenza A, another enveloped virus. These results show that fatty acid synthesis is essential for the replication of two divergent enveloped viruses and that systems-level metabolic flux profiling can identify metabolic targets for antiviral therapy.
- Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
- Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 712, Rochester, New York 14642, USA
- Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Carl Icahn Laboratory, Princeton University, Princeton, New Jersey 08544, USA
- Department of Chemistry, Frick Laboratory, Princeton University, Princeton, New Jersey 08544, USA
- These authors contributed equally to this work.
Correspondence to: Joshua D Rabinowitz3 e-mail: joshr@genomics.princeton.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Research highlightsNature Chemical Biology News and Views (01 Nov 2008)
From biomarkers to integrated network responsesNature Biotechnology News and Views (01 Oct 2008)
RESEARCH
Energy Metabolism in Astrocytes and Neurons Treated With Manganese: Relation Among Cell-Specific Energy Failure, Glucose Metabolism, and Intercellular Trafficking Using Multinuclear NMR-Spectroscopic AnalysisJournal of Cerebral Blood Flow & Metabolism Original Article
Measurement of the Tricarboxylic Acid Cycle Rate in Human Grey and White Matter in Vivo by 1 H-[ 13 C] Magnetic Resonance Spectroscopy at 4.1TJournal of Cerebral Blood Flow & Metabolism Original Article
See all 24 matches for Research
