4january2018|VOL553|naTurE|77LETTErdoi:10.1038/nature25140SootymangabeygenomesequenceprovidesinsightintoAIDSresistanceinanaturalSIVhostDavidPalesch1*,StevenE.Bosinger1,2*,GregoryK.Tharp1,ThomasH.Vanderford1,MirkoPaiardini1,2,annChahroudi1,3,ZacharyP.johnson1,FrankKirchhoff4,BeatriceH.Hahn5,robertB.norgrenjr6,niravB.Patel1,DonaldL.Sodora7,reema.Dawoud1,Caro-BethStewart8,SaraM.Seepo8,r.alanHarris9,10,yueLiu9,Muthuswamyraveendran9,10,yiHan9,adamEnglish9,GreggW.C.Thomas11,MatthewW.Hahn11,LenorePipes12,ChristopherE.Mason12,DonnaM.Muzny9,10,richarda.Gibbs9,10,DanielSauter4,KimWorley9,10,jeffreyrogers9,10&GuidoSilvestri1,2Incontrasttoinfectionswithhumanimmunodeficiencyvirus(HIV)inhumansandsimianimmunodeficiencyvirus(SIV)inmacaques,SIVinfectionofanaturalhost,sootymangabeys(Cercocebusatys),isnon-pathogenicdespitehighviraemia1.Herewesequencedandassembledthegenomeofacaptivesootymangabey.Weconductedgenome-widecomparativeanalysesoftranscriptassembliesfromC.atysandAIDS-susceptiblespecies,suchashumansandmacaques,toidentifycandidatesforhostgeneticfactorsthatinfluencesusceptibility.Weidentifiedseveralimmune-relatedgenesinthegenomeofC.atysthatshowsubstantialsequencedivergencefrommacaquesorhumans.Oneofthesesequencedivergences,aC-terminalframeshiftinthetoll-likereceptor-4(TLR4)geneofC.atys,isassociatedwithabluntedinvitroresponsetoTLR-4ligands.Inaddition,wefoundamajorstructuralchangeinexons3–4oftheimmune-regulatoryproteinintercellularadhesionmolecule2(ICAM-2);expressionofthisvariantleadstoreducedcellsurfaceexpressionofICAM-2.ThesedataprovidearesourceforcomparativegenomicstudiesofHIVand/orSIVpathogenesisandmayhelptoelucidatethemechanismsbywhichSIV-infectedsootymangabeysavoidAIDS.SIVinfectionofnaturalhosts,suchassootymangabeys,istypicallynon-pathogenicdespitehighviraemia.ThisisinstarkcontrasttoHIVinfectioninhumansandexperimentalSIVinfectioninrhesusmacaques(Macacamulatta)thatprogresstoAIDSunlesstreatedwithantiretroviraltherapy.Themainvirologicalandimmunologicalfea-turesofnaturalSIVinfe...
