Differences in APOBEC3G Expression in CD4+ T Helper Lymphocyte Subtypes Modulate HIV-1 Infectivity 英文参考文献.docVIP

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Differences in APOBEC3G Expression in CD4+ T Helper Lymphocyte Subtypes Modulate HIV-1 Infectivity 英文参考文献.doc

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DifferencesinAPOBEC3GExpressioninCD4THelperLymphocyteSubtypesModulateHIV-1Infectivity英文参考文献

DifferencesinAPOBEC3GExpressioninCD4+THelper LymphocyteSubtypesModulateHIV-1Infectivity MichaelL.Vetter1,MeganE.Johnson1,AmandaK.Antons1,DeryaUnutmaz2,RichardT.D’Aquila1,3* 1Department of Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, United States of America, 2Department of Microbiology, New York University,NewYork,NewYork,UnitedStatesofAmerica,3DepartmentofMedicine,DivisionofInfectiousDiseases,VanderbiltUniversity,Nashville,Tennessee,United StatesofAmerica Abstract The cytidine deaminases APOBEC3G and APOBEC3F exert anti–HIV-1 activity that is countered by the HIV-1 vif protein. Based on potential transcription factor binding sites in their putative promoters, we hypothesized that expression of APOBEC3G and APOBEC3F would vary with T helper lymphocyte differentiation. Naive CD4+ T lymphocytes were differentiated to T helper type 1 (Th1) and 2 (Th2) effector cells by expression of transcription factors Tbet and GATA3, respectively,aswellasbycytokinepolarization.APOBEC3GandAPOBEC3FRNAlevels,andAPOBEC3Gproteinlevels,were higherinTh1thaninTh2cells.TcellreceptorstimulationfurtherincreasedAPOBEC3GandAPOBEC3FexpressioninTbet- andcontrol-transduced,butnotinGATA3-transduced,cells.Neutralizinganti–interferon-cantibodiesreducedbothbasal andTcellreceptor-stimulatedAPOBEC3GandAPOBEC3FexpressioninTbet-andcontrol-transducedcells.HIV-1produced fromTh1cellshadmorevirionAPOBEC3G,anddecreasedinfectivity,comparedtovirionsproducedfromTh2cells.These differencesbetweenTh1-andTh2-producedvirionsweregreaterforviruseslackingfunctionalvif,butalsoseenwithvif- positiveviruses.Over-expressionofAPOBEC3GinTh2cellsdecreasedtheinfectivityofvirionsproducedfromTh2cells,and reductionofAPOBEC3GinTh1cellsincreasedinfectivityofvirionsproducedfromTh1cells,consistentwithacausalrolefor APOBEC3G in the infectivity difference. These results indicate that APOBEC3G and APOBEC3F levels vary physiologically during CD4+ T lymphocyte differentiation, that interferon-c contributes to this