| Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. | |
| | |
MedLine Citation:
|
PMID: 18820684 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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 (13)C-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. |
| | |
Authors:
|
Joshua Munger; Bryson D Bennett; Anuraag Parikh; Xiao-Jiang Feng; Jessica McArdle; Herschel A Rabitz; Thomas Shenk; Joshua D Rabinowitz |
Related Documents
:
|
8511174 - Dietary amino acid complementation as a foraging strategy for wild birds. 20505134 - Clinical and biochemical features of aromatic l-amino acid decarboxylase deficiency. 6851934 - The effect of methyl oleate hydroperoxide, a possible toxic ozone intermediate, on huma... 1959624 - Inhibition by lipoxygenase-3 of n-hexanal generation in soybeans. 1091854 - Effects of p-fluorophenylalanine on the induction of mutations in bacteriophage t4. i. ... 11535084 - Helical ribbon aggregate composed of a crown-appended cholesterol derivative which acts... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2008-09-28 |
Journal Detail:
|
Title: Nature biotechnology Volume: 26 ISSN: 1546-1696 ISO Abbreviation: Nat. Biotechnol. Publication Date: 2008 Oct |
Date Detail:
|
Created Date: 2008-10-10 Completed Date: 2008-12-29 Revised Date: 2012-01-17 |
Medline Journal Info:
|
Nlm Unique ID: 9604648 Medline TA: Nat Biotechnol Country: United States |
Other Details:
|
Languages: eng Pagination: 1179-86 Citation Subset: IM |
Affiliation:
|
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antiviral Agents / administration & dosage* Biological Markers / metabolism Computer Simulation Cytomegalovirus / drug effects, metabolism* Drug Delivery Systems / methods Fatty Acids / metabolism* Humans Models, Biological Signal Transduction / drug effects, physiology* Systems Integration |
| Grant Support | |
ID/Acronym/Agency:
|
5 P50 GM071508/GM/NIGMS NIH HHS; AI068678/AI/NIAID NIH HHS; CA82396/CA/NCI NIH HHS; CA85786/CA/NCI NIH HHS; P50 GM071508-01/GM/NIGMS NIH HHS; R01 AI078063-03/AI/NIAID NIH HHS; R01 CA082396-11/CA/NCI NIH HHS; R01 CA082396-14/CA/NCI NIH HHS; R01 CA085786-01/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antiviral Agents; 0/Biological Markers; 0/Fatty Acids |
| Comments/Corrections | |
Comment In:
|
Nat Biotechnol. 2008 Oct;26(10):1090-2
[PMID:
18846075
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Modulation of the antitumor immune response by complement.
Next Document: Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum.