Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy

By Joshua C. Munger, Bryson D. Bennett, Anuraag S. Parikh, Xiao-Jiang Feng, Jessica McArdle, Herschel A. Rabitz, T. Shenk, Joshua D. Rabinowitz. Nature Biotechnology, 2008

638 citations recorded by the source corpus.

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.

Subfields: Clinical Biochemistry, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/98e426c927abdd6af1da9cd6e6a04168cc435dde

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Clinical Biochemistry

1. Joshua D. Rabinowitz
2. M. V. Vander Heiden

In Epidemiology

1. Craig B. Thompson
2. G. Randall
3. Nicholas S. Heaton
4. Joshua D. Rabinowitz
5. Beth Levine
6. Guido Kroemer

In Molecular Biology

1. M. V. Vander Heiden
2. Craig B. Thompson
3. Joshua D. Rabinowitz
4. Patrick S. Ward
5. Lewis C. Cantley
6. S. Y. Chan
7. Ralph J. Deberardinis
8. Joseph Loscalzo

Citations in the corpus

• Dengue virus induced autophagy regulates lipid metabolism (2010, background): “Cytomegalovirus infection profoundly alters cellular metabolism, including increases in fatty acid synthesis, glycolysis, the citric acid cycle, and nucleotide biosynthesis (Munger et al., 2006; Munger et al., 2008).”
• The Emerging Paradigm of Network Medicine in the Study of Human Disease (2012, background): “88 Subsequent pharmacological targeting of fatty acid biosynthesis suppressed the replication of HCMV and influenza A, thereby confirming that fatty acid synthesis is essential for the replication of two divergent viruses and, importantly, that systems-level metabolic flux profiling can identify…”
• Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. (2015, neutral): “dance of C and N metabolites (Munger et al., 2008).”
• Cancer-associated IDH1 mutations produce 2-hydroxyglutarate (2009, positive): “Metabolite flux studies from 13 C-glutamine were performed as described previously 21 .”