Silibinin Inhibits HIV-1 Infection by Reducing Cellular Activation and Proliferation 英文参考文献.docVIP

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Silibinin Inhibits HIV-1 Infection by Reducing Cellular Activation and Proliferation 英文参考文献.doc

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Silibinin Inhibits HIV-1 Infection by Reducing Cellular Activation and Proliferation 英文参考文献

SilibininInhibitsHIV-1InfectionbyReducingCellular ActivationandProliferation JanelaMcClure1,EricaS.Lovelace1,ShokrollahElahi6,NicholasJ.Maurice5,JessicaWagoner1, JoanDragavon1,JohnE.Mittler4,ZaneKraft6,LeonidisStamatatos3,6,HelenHorton6,StephenC.De Rosa1,5,RobertW.Coombs1,2,StephenJ.Polyak1,3,4 * 1Department ofLaboratoryMedicine,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica, 2Department ofMedicine,UniversityofWashington, Seattle,Washington,UnitedStatesofAmerica,3DepartmentofGlobalHealth,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica,4Departmentof Microbiology, University of Washington, Seattle, Washington, United States of America, 5Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center,Seattle,Washington,UnitedStatesofAmerica,6ViralVaccinesProgram,SeattleBiomed,Seattle,Washington,UnitedStatesofAmerica Abstract Purified silymarin-derived natural products from the milk thistle plant (Silybum marianum) block hepatitis C virus (HCV) infectionandinhibitTcellproliferationinvitro.Anintravenousformulationofsilibinin(SIL),amajorcomponentofsilymarin, displaysanti-HCVeffectsinhumansandalsoinhibitsT-cellproliferationinvitro.WeshowthatSILinhibitedreplicationof HIV-1inTZM-blcells,PBMCs,andCEMcellsinvitro.SILsuppressionofHIV-1coincidedwithdose-dependentreductionsin activelyproliferatingCD19+,CD4+,andCD8+cells,resultinginfewerCD4+TcellsexpressingtheHIV-1co-receptorsCXCR4 andCCR5.SILinhibitionofT-cellgrowthwasnotduetocytotoxicitymeasuredbycellcyclearrest,apoptosis,ornecrosis.SIL alsoblockedinductionoftheactivationmarkersCD38,HLA-DR,Ki67,andCCR5onCD4+Tcells.ThedatasuggestthatSIL attenuatedcellularfunctionsinvolvedinT-cellactivation,proliferation,andHIV-1infection.Silymarin-derivedcompounds providecytoprotectionbysuppressingvirusinfection,immuneactivation,andinflammation,andassuchmayberelevant forbothHIVmono-infectedandHIV/HCVco-infectedsubjects. Citation: McClure J, Lovelace ES, Elahi S, Maurice NJ, Wagoner J, et al