Divergent Effects of Human Cytomegalovirus and Herpes Simplex Virus-1 on Cellular Metabolism 英文参考文献.docVIP

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Divergent Effects of Human Cytomegalovirus and Herpes Simplex Virus-1 on Cellular Metabolism 英文参考文献.doc

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Divergent Effects of Human Cytomegalovirus and Herpes Simplex Virus-1 on Cellular Metabolism 英文参考文献

DivergentEffectsofHumanCytomegalovirusandHerpes SimplexVirus-1onCellularMetabolism LiviaVastag1,EmreKoyuncu2,SarahL.Grady2,ThomasE.Shenk2,JoshuaD.Rabinowitz1* 1DepartmentofChemistry,PrincetonUniversity,Princeton,NewJersey,UnitedStatesofAmerica,2DepartmentofMolecularBiology,PrincetonUniversity,Princeton, NewJersey,UnitedStatesofAmerica Abstract Viruses rely on the metabolic network of the host cell to provide energy and macromolecular precursors to fuel viral replication.Hereweusedmassspectrometrytoexaminetheimpactoftworelatedherpesviruses,humancytomegalovirus (HCMV) and herpes simplex virus type-1 (HSV-1), on the metabolism of fibroblast and epithelial host cells. Each virus triggeredstrongmetabolicchangesthatwereconservedacrossdifferenthostcelltypes.Themetaboliceffectsofthetwo viruses were, however, largely distinct. HCMV but not HSV-1 increased glycolytic flux. HCMV profoundly increased TCA compound levels and flow of two carbon units required for TCA cycle turning and fatty acid synthesis. HSV-1 increased anapleuroticinfluxtotheTCAcyclethroughpyruvatecarboxylase,feedingpyrimidinebiosynthesis.Thus,thesetworelated herpesvirusesdrivediversehostcellstoexecutedistinct,virus-specificmetabolicprograms.Currentdrugstargetnucleotide metabolismfortreatmentofbothviruses.AlthoughourresultsconfirmthatthisisarobusttargetforHSV-1,therapeutic interventionsatotherpointsinmetabolismmightprovemoreeffectivefortreatmentofHCMV. Citation:VastagL,KoyuncuE,GradySL,ShenkTE,RabinowitzJD(2011)DivergentEffectsofHumanCytomegalovirusandHerpesSimplexVirus-1onCellular Metabolism.PLoSPathog7(7):e1002124.doi:10.1371/journal.ppat.1002124 Editor:MichaelLagunoff,UniversityofWashington,UnitedStatesofAmerica ReceivedFebruary24,2011;AcceptedMay3,2011;PublishedJuly14,2011 Copyright: ? 2011 Vastag et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsou