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Metabolomic Profile of Hepatitis C Virus-Infected Hepatocytes 英文参考文献
MetabolomicProfileofHepatitisCVirus-Infected
Hepatocytes
BarbaraRoe1*,ElizabethKensicki2,RobertMohney2,WilliamW.Hall1
1CentreforResearchinInfectiousDiseases,SchoolofMedicineandMedicalScience,UniversityCollegeDublin,Belfield,Dublin,Ireland,2MetabolonInc.,Durham,North
Carolina,UnitedStatesofAmerica
Abstract
HepatitisCvirus(HCV)iscapableofdisruptingdifferentfacetsoflipidmetabolismandlipidshavebeenshowntoplaya
crucial role in the viral life cycle. The aim of this study was to examine the effect HCV infection has on the hepatocyte
metabolome. Huh-7.5 cells were infected using virus produced by the HCV J6/JFH1 cell culture system and cells were
harvested 24, 48, and 72-hours following infection. Metabolic profiling was performed using a non-targeted multiple
platformmethodologycombiningultrahighperformanceliquidchromatography/tandemmassspectrometry(UHPLC/MS/
MS2) and gas chromatography/mass spectrometry (GC/MS). There was a significant increase in a number of metabolites
involvedinnucleotidesynthesisandRNAreplicationduringearlyHCVinfection.NADlevelswerealsosignificantlyincreased
along with several amino acids. A number of lipid metabolic pathways were disrupted by HCV infection, resulting in an
increaseincholesterolandsphingolipidlevels,alteredphospholipidmetabolismandapossibledisruptioninmitochondrial
fattyacidtransport.Fluctuationsin59-methylthioadenosinelevelswerealsonoted,alongwithalterationsintheglutathione
synthesispathway.Theseresultshighlightanumberofpreviouslyunreportedmetabolicinteractionsandgiveamorein
depthinsightintotheeffectHCVhasonhostcellbiochemicalprocesses.
Citation: Roe B, Kensicki E, Mohney R, Hall WW (2011) Metabolomic Profile of Hepatitis C Virus-Infected Hepatocytes. PLoS ONE 6(8): e23641. doi:10.1371/
journal.pone.0023641
Editor:RaviJhaveri,DukeUniversity,UnitedStatesofAmerica
ReceivedMay12,2011;AcceptedJuly21,2011;PublishedAugust11,2011
Copyright:?2011Roeetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicens
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