SAMHD1's protein expression profile in humans

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: innate immunity;    restriction factor;    HIV;    HSV;   

DOI  :  10.1189/jlb.4HI0714-338RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Thedeoxynucleosidetriphosphatetriphosphohydrolaseand3′→5′exonucleaseSAMHD1restrictsHIV‐1infectioninnoncyclinghematopoieticcellsinvitro,andSAMHD1mutationsareassociatedwithAGS.Littleisknownabouttheinvivoexpressionandfunctionalregulationofthiscellularfactor.Here,wefirstassessedtheSAMHD1proteinexpressionprofileonamicroarrayof25humantissuesfrom>210donorsandinpurifiedprimarycellpopulations.Invivo,SAMHD1wasexpressedinthemajorityofnucleatedcellsofhematopoieticorigin,includingtissue‐residentmacrophages,DCs,pDCs,alldevelopmentalstagesofthymicTcells,monocytes,NKcells,aswellasatlowerlevelsinBcells.Ofnote,SAMHD1wasabundantlyexpressedinHIVtargetcellsresidingintheanogenitalmucosa,providingabasisforitsevaluationasacellularfactorthatmayimpacttheefficiencyofHIVtransmission.Next,weexaminedtheeffectoftheactivationstatusandproinflammatorycytokinetreatmentofcellsonexpressionandphosphorylationofSAMHD1.Activated,HIV‐susceptibleCD4+TcellscarriedpSAMHD1(T592),whereasrestingCD4+TcellsandmacrophagesexpressedtheunphosphorylatedproteinwithHIV‐restrictiveactivity.Surprisingly,stimulationoftheseprimarycellswithIFN‐α,IFN‐γ,IL‐4,IL‐6,IL‐12,IL‐18,IL‐27,orTNF‐αaffectedneitherSAMHD1expressionlevelsnorthreonine592phosphorylation.OnlyIL‐1βmoderatelydown‐regulatedSAMHD1inactivatedCD4+Tcells.Takentogether,thisstudyestablishesthefirstcross‐sectionalproteinexpressionprofileofSAMHD1inhumantissuesandprovidesinsightintoitscellcycle‐dependentphosphorylationandunresponsivenesstomultipleproinflammatorycytokines...

【 授权许可】

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