topological perspective on hiv escape andrew j. mcmichael资料.pdf

该【topological perspective on hiv escape andrew j. mcmichael资料 】是由【宝钗文档】上传分享，文档一共【3】页，该文档可以免费在线阅读，需要了解更多关于【topological perspective on hiv escape andrew j. mcmichael资料 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。INSIGHTS|-profilesdifferedfromthoseofmaturement,suchrecognitionsystemsmostlikelyeurons(11),highlightingworkinconcertwithamultitudeofinter-Topologicaltheimportanceofthedevelopmentalap-sectingregulatorymechanisms,-spatiotemporalregulationofconnectivityspecifictranscriptsencodeproteinsrelatedpatternformation(14),localposttranscrip-perspectiveontosynapticprocessesand/orsynaptogen-tionalregulation,(15).(Cbln4),leucine-(Lgi2),-Anetworkanalysisexplains(Fgf13)asselectivelyexpressedindevel-anizersworkinopingsomatostatin-positivecells,parval-concerttoachievereproduciblesynapsevariabilityinimmunebumin-positivebasketcells,,respectively(allGABAergic).-1infectionhasavari--DownloadedfromLocalexpressionofthephosphatasePrl-1(orange)isamechanismthatcontrolsgresstoAIDSwithinafewmonths,;-Usionisaffectedbyvariationinthegenesthatencodeapatient’shumanleukocytehttp://science./antigen(HLA)proteins(1–3).Thisge-neticassociationbetweenHLAandAIDSprogressionhasbeenattributedtodiffer-encesinTcellrecognitionofHLA-boundHIV-(4).Onpage480ofthisissue,neuronPrl-1activatesasignalingGaihaetal.(5)explainvariationinHIVpathwayrequiredforimmuneescapebyexaminingeachepitopesynaptogenesisinaspecifcaxonalinthecontextofHIVproteinstructure,us-onMay2,-idswithmultipleinteractionswithinthethree-dimensionalstructureofanHIVpro-teinareconstrainedfromescapeandtendCbln4ismostenrichedinsomatostatin--.,Science351,aaa5694(2016)..,Science364,eaau9952(2019).infectedcellsdisplayandpresentHIV-.,Science363,413(2019).+.,,7143(2006).-anizetranssynap-,,ülow,,271ablesCD8+TcellstorecognizetheseHIVplexesbetweenpostsynapticrecep-(2015)..,Cell166,181(2016)..,Neuron95,852(2017).Becausesomeepitopesareconstrainedproteins(12,13).,,,,eLife7,andcannotmutatewithoutaffectingviralinparvalbumin-eu-e36697(2018).fitness,,,,370(2005)..,CancerCell18,52(2010).particularpeptidesaremoreeffectiveinpartmentofpyramidalneu-.,Cell171,522(2017).,,191(2010).,üdhof,,4774(2018).,,Cell163,285(2015).,,,,,-,136(2017).,SCIENCEtostatin-.-SupportedbytheSwissNationalScienceFoundationandERCpartmentalizationisgovernedbyache-,UniversityofOxford,,themolecularSchmuckerforhelpwiththeillustrationandA.-NDMResearchBuilding,OldRoadCampus,OxfordOX37FZ,,FrederickNationalLaboratoryrepertoireofindividualneuronclasseswouldforCancerResearch,Frederick,MD21702,:andrew.******@;******@:4383MAY2019?SCIENCEPublishedbyAAASsimplybecausetheyarenottar-ConnectionsanalysisSIVinfectionsoonafterexperi-getedbytheimmuneresponseQuantificationofinterconnectivitybetweenaminoacidswithineachHIVproteinmentalchallenge(in>50%)(13).However,,+Tcellresponseselic-ine,includingunderstood,butclearly,somerestrictionofresponsesbyma-HLApolymorphismplexmoreimmunogenicthanoth-(MHC)classIIandbynonclas--E,aswellastypes(suchasB*57,B*27,andHIV-1–infectedcellCD8+TcellstheexceptionalbreadthoftheB*81)tendtobindtomorecon-(bearingHLA-peptide(immunodominant)Tcellresponses(vertebrateservedpeptideepitopes,plex)MHCincludeshumanHLAandmayincurfitnesscostsiftheymonkeyMamu).Itisunlikelymutate(6,7).However,workthattheinfectingSIVcouldmeansareallinfectedpeopleanalysisofHIVepitopesescapefromTcellsthatrecog-andmutationswiththese“lucky”HLAtypesnizemultipleSIVepitopesatprotected,andsomewhoat-,afocusonworkedorconservedepi--(anHIV-1protein)-1proteins,workscoreotherhand,ine-stimulated(Leu83–>Met(Pro34–>Ala+-inepitopeAV9)epitopeKF11)workedepi-topes,typically8to11aminotopesofHIV-1maybevalu-acidslong,foritscontactsableintherapeuticstrategies,http://science./Fitnesscostwithotheraminoacidsintheallowingthepatienttoeradi-+TcellsNoescapefromDecreasedhydrogenbonds,vanderWaalsCD8+ereactivated(14).contacts,saltbridges,disul-hatfocusesTcellphidebonds,cation-pinter-workedactions,metalcoordinatedepitopes,whichareoftennotbonds,andlocalhydrophobicPoorviralcontrolViralcontrolnaturallyimmunodominant,-—,,,,131(2012).onMay2,2019validatedthisapproachwithnon-HIVpro-.,Science317,944(2007)..,Science330,1551(2010).showedhighlysignificantinversecorrela-.,Nature354,453(1991).workscoreandexperi-.,Science364,480(2019)..,,12937(2014).Therefore,,Retrovirology1,8(2004)..,,11530uratemeasureoffit-evenmoreinformativebecausevariation(2011)..,Immunity38,606(2013).-.,,11660(2016).theprotectivevalueofallwell-definedpep-munodominance,.,,380(2013)..,Immunity12,83(2000).tideepitopesandcorrelatedthiswiththethatstimulatesthestrongestTcellre-.,Nature502,100(2013).strengthofTcellresponsestothatpeptidesponseexertsthestrongestselectivepres-.,Nature517,381(2015).andthecontrolofviremia(seethefigure).sure(11).petewithACKNOWLEDGMENTSThefindingsprovideanexplanationforandsuppresslessfrequentTcells,-(NIH)–NationalthebasisofHLAtypeandclarifywhysomedominateandwhythisvariesbetweenin-InstituteofAllergyandInfectiousDiseasesCenterforHIV/peoplewithout“good”HLAmoleculescandividuals(12).InthecontextofHIVinfec-ineImmunologyandImmunogenDiscovery(UM1AI00645)andtheMedialResearchCouncilUK(K012037/1).havegoodimmunecontroloverinfection,tionandepitopefitness,(HHSN261200800001E)andtheIntramuralResearchHLAtypes,whoseTcellsfocusonlesscon-,FrederickNationalLab,,donotcontrolHIV--,,(8–10).Ratherthantherus(SIV)/HIV–specificTcell–stimulatingNIH,FrederickNationalLab,-inehasbeenshowntobeGRAPHIC::etal.,thesestudiesusedstatisticalcorre-?(6439),438-:://science./content/364/6439/438RELATEDhttp://science./content/sci/364/6439/://science./REFERENCESThisarticlecites14articles,essforfreehttp://science./content/364/6439/438#BIBLPERMISSIONSp/reprints-and-permissionsonMay2,2019UseofthisarticleissubjecttotheTermsofServiceScience(printISSN0036-8075;onlineISSN1095-9203)ispublishedbytheAmericanAssociationfortheAdvancementofScience,1200NewYorkAvenueNW,Washington,?TheAuthors,somerightsreserved;.