Document Detail


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
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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:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  9604648     Medline TA:  Nat Biotechnol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1179-86     Citation Subset:  IM    
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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/GM/NIGMS NIH HHS; P50 GM071508-01/GM/NIGMS NIH HHS; R01 AI078063/AI/NIAID NIH HHS; R01 AI078063-03/AI/NIAID NIH HHS; R01 CA082396/CA/NCI NIH HHS; R01 CA082396-11/CA/NCI NIH HHS; R01 CA085786/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 ]

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