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1、LETTERdoi:10.1038/nature10718T-celldifferentiationfactorCBF-bregulatesHIV-1Vif-mediatedevasionofhostrestriction11,2221,2WenyanZhang*,JuanDu*,SeanL.Evans,YunkaiYu&Xiao-FangYuThehumanAPOBEC3cytidinedeaminasesarepotentinhibitorsinteractionbetweenHIV-1Vif–HAandCBF-bintransfected293Tofdiverseretro
2、viruses,includinghumanimmunodeficiencyvirus-1(humanembryonickidney)cells(Fig.1c,lane4),indicatingthatthe1–6(HIV-1).HIV-1VifformsanE3ubiquitinligasecomplexwithinteractionbetweenCBF-bandHIV-1Vifcanoccurintheabsenceof7–9cullin5(CUL5),elonginBandelonginC,whichpromotesthepolyubiquitinationanddegra
3、dationofAPOBEC3substrates7,10–14.ad+++–––siRNAcontrol–––+++CBF-βsiRNAHerewedemonstrateinhumanTcellsthatcorebindingfactorb90++++++A3G–HACUL5–+––+–NL4-3ΔVif(CBF-b)isakeyregulatoroftheevasionofHIV-1fromthehost––+––+NL4-3defencemediatedbyAPOBEC3.CBF-b,thenon-DNA-bindingPr55Gag50subunitofaheterodi
4、merictranscriptionfactor,regulatesthefoldingA3G–HA36VifandDNA-bindingactivityofpartnerRUNXfamilyproteins,which29CBF-βhaveimportantrolesinthedevelopmentanddifferentiationofVif–HARibosomalp1915,16123456diversecelltypes,includingTlymphocytes.Inourstudy,knock-CBF-β21CelllysatedownofendogenousCBF-
5、bblockedVif-inducedAPOBEC3Gpolyubiquitinationanddegradation.CBF-bwasnotrequiredeA3G–HA12CAp24fortheinteractionbetweenVifandAPOBEC3G,yetwasessentialIP:anti-HA123456fortheassemblyoftheVif–CUL5E3-ubiquitin-ligasecomplex.VirusbCUL5fCBF-bprovedtobeauniqueregulatorofprimatelentiviralVif120A3G+andno
6、tageneralcomponentoftheCUL5E3ubiquitinligase.WeVif–HA10080NL4-3+A3GshowthatVifandCBF-bphysicallyinteract,andthattheamino-CBF-β60NL4-3ΔVif+A3GELOBRelative40terminalregionofVifisrequiredforthisinteraction.Furthermore,20ELOCinfectivity(%)0ControlCBF-βinteractionswithVifrequiredregionsinCBF-bthat
7、arenotinvolved12siRNAsiRNAinRUNXproteinbinding17–19.ConsideringtheimportanceoftheIP:anti-HA1234interactionbetweenVifandCBF-b,disruptingthisinteractiongA3G–c+–+–VR1012representsanattractivepharmacologicalinterventionagainst–+–+HIV–1Vif–HA12010
