SAMHD1's protein expression profile in humans

[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...

[学科分类] 生理学

[关键词] innate immunity;restriction factor;HIV;HSV