HIV英文专业知识讲座

Retroviruses1第1页PropertiessharingwithRetroviridae

1.Twocopiesoflinear+ssRNA,covalentlylinked2.Possessreversetranscriptase(RT)3.Enveloped4.Spherical,80-100nm2第2页RetroviridaeThreesubfamilies:1.Oncovirinae:RNAtumorvirusesHumanTLymphotropicVirus1causesT-cellleukemia/lymphomacausesHTLV-associatedmyelopathy(HAM)2.Spumavirinae:foamyvirusesNonpathogenichumanretroviruses3.Lentivirinae:slowvirusesHIV-1and2:causeAIDS3第3页HumanImmunodeficiencyVirus(HIV)4第4页OutlineI.EpidemiologyII.BiologicalpropertiesStructureGenomeandproteins：gp120,gp41Replication：receptor，provirus5第5页III.PathogenesisandimmunityTransmissionroutesPathogenesis：targetcellsClinicalfeaturesIV.Laboratorydiagnosis：detectionofAbV.Treatment：HAART6第6页I.Epidemiology7第7页History1981,5casesofPneumocystiscariniipneumoniainUSA,allmalehomosexualAcquiredimmunodeficiencysyndromeIsolationofthevirusin1983

and1984NamedasHIVin19868第8页FrançoiseBarré-SinoussiLucMontagnier

Laureatesof2023Nobelprizeinphysiologyormedicine9第9页HIVVirusesTwotypesofHIVviruses:HIV-1responsibleforaworldwidepandemicthathasinfected≥40millionHIV-2mostlylimitedtoWesternandCentralAfricawithfewercases10第10页(A)HIV-1originatedfromasinglesubspeciesofthechimpanzee,Pantroglodytestroglodytes(B)HIV-2originatedfromthesootymangabey,Cercocebusatys(白颈白眉猴)11第11页HIV-1PrevalenceRatebyCountrymodifiedfromWHOmap,2023data12第12页II.Biologicalproperties13第13页14第14页StructureofHIVVirionEnvelopeCapsid:bulletshapedNucleicacid:2identicalsegmentsof+ssRNA3importantenzymesreversetranscriptaseintegraseprotease15第15页HIVEnvelopeSurfaceglycoproteins:gp120:interactwithreceptoronthecellgp41:fusogenthatisexposedaftergp120hasboundtothecell16第16页POL:EnzymesReversetranscriptaseIntegraseProtease(cutspolyproteins)

ThreestructuralgenesGAG:internalproteinsENV:Envelopeglycoproteins17第17页HIVgenomegaggenecodesfornucleocapsidproteinsenvgenecodesforenvelopeglycoproteins,i.e.gp41(transmembraneprotein)andgp120(surfaceprotein)polgenecodesforenzymessuchasreversetranscriptase,proteaseandintegraseOthergenescodeforvariousactivatorsandaccessoryproteins18第18页ReplicationofHIV19第19页HIVReceptorsCD4receptor:

FoundonCD4+Thelpercells,monocytes,anddendriticcells.PrimaryreceptorusedbyHIV–1Coreceptor(CCR5orCXCR4):

chemokinereceptorfoundonlymphocytesandmonocytes.

Gp120:GP120bindstotheCD4receptorthenthechemokineco-receptorontheTcell.20第20页gp12021第21页Step2FusionanduncoatingHIVtransmembraneprotein(gp41)undergoesachangeallowingittobindtotheCCR5co-receptorGp41injectsthefusionpeptideintothecellmembraneFusionofHIVandcellularmembranesReleaseofnucleocapsidtocytoplasm22第22页23第23页ParentalRNA

RNA/DNAHybrid

LinearDNA/DNAduplexCircularDuplexDNA

Integration Replication(DNAgenomeincell)Transcription ViralRNAgenome mRNA protein

ReversetranscriptaseReversetranscriptaseIntegraseHostRNApolIIHostDNApolymeraseHostsplicingenzymes24第24页HIVReverseTranscriptaseThereversetranscriptaseiserror-prone:alotofmutationsareintroducedduringreplication,whichincreasesHIVgeneticvariation.HIVreplicatesveryquickly(10billionnewvirionsaday),whichcombinedwiththehighrateofmutationleadsto“acceleratedevolution”andtheappearanceof“quasi-species”25第25页ReverseTranscriptaseInhibitorsA.Nucleosidereversetranscriptaseinhibitors(NRTIs)

incorporatedintheelongatingDNAchainformedfromthegenomicRNA,andterminatetheelongation(chainterminators)26第26页ReverseTranscriptaseInhibitorsB.Nonnucleosidereversetranscriptaseinhibitors(NNRTIs):bindintoapocketwithinasubunitoftheenzyme,changingtheconformationoftheRTandinhibitingitsactivity27第27页28第28页IntegraseInhibitorRaltegravirwasrecentlyapproved,highlyeffectiveandwelltolerated29第29页Step5ProviraltranscriptionProvirusmRNAStep6TranslationmRNAprotein30第30页HIVProtease31第31页Step8Assembly,maturationandrelease32第32页Pathogenesisandimmunity33第33页HowHIVcanbetransmittedSex:

Unprotectedsexualcontact–beitvaginal,oral,oranal-withaninfectedpartnerBlood:BysharingunsterilizedneedlesorsyringeswithanHIVpositiveperson,forexample,throughbloodtransfusionswithinfectedblood.Mother-to-Child:

Duringpregnancyorbirthandthroughbreastfeeding34第34页HowHIVcanNOTbetransmittedThroughairorbycoughingandsneezingThroughfoodorirrigateThroughsweatandtearsBysharingcups,plates,andutensilswithaninfectedpersonBytouching,huggingandkissinganinfectedpersonBysharingclothesorshakinghandswithaninfectedpersonBysharingtoiletsandbathroomswithaninfectedpersonBylivingwithaninfectedpersonBymosquitoes,fleas,orotherinsects35第35页TargetcellsHIVcaninfectavarietyofimmunecells:CD4+Tcells,macrophages,dentridiccellsmicroglialcells（小胶质细胞）.36第36页FromHIVInfectiontoAIDS37第37页InfectionwithHIV-1isassociatedwithaprogressivedecreaseoftheCD4+Tcellcountandanincreaseinviralload.38第38页CD4+Tcellcount(cellsperµL)

HIVRNAcopiesper

mLofplasma39第39页StagesofHIVinfectionPrimaryinfectionAsymptomaticinfectionAIDS40第40页PrimaryinfectionInitialincubationperiod:

usuallylastsbetweentwoandfourweeks.Acuteinfection:lastsanaverageof28daysandcanincludesymptoms:fever,lymphadenopathy(swollenlymphnodes),pharyngitis(sorethroat),rash,myalgia(musclepain),malaise,andmouthandesophagealsores.41第41页42第42页Asymptomaticinfection

/latencystageShowsfewornosymptomsAveragetimespan:about10years43第43页AIDSConstitutionalsymptomsWhenCD4+Tcellnumbersdeclinebelowacriticallevelof200cellsperµL,cell-mediatedimmunityislost

showsassymptomsofvariousopportunisticinfections.Malignanttumors44第44页Thefirstsymptomsofteninclude:weightloss,recurringrespiratorytractinfections(suchassinusitis,bronchitis,otitismedia,pharyngitis),prostatitis,skinrashesoralulcerations.45第45页Opportunisticinfections(OIs):

oralcandidiasis(thrush)鹅口疮PneumocystiscariniipneumoniaTuberculosisHerpesvirusinfectionsEtc.46第46页oralcandidiasis(thrush)47第47页Pneumocystiscarinii

pneumonia(interstitialpneumonia)

Pneumocystiscarinii

48第48页AIDS-associatedcancers:

Kaposisarcomanon-Hodgkinlymphoma.Hodgkindiseaseandcancersofthelung,mouth,cervix,anddigestivesystemWastingsyndrome:“slimdisease”49第49页Kaposi’s

Sarcoma

（多发性特发性出血性肉瘤）

50第50页Laboratorydiagnosis51第51页TestofspecificAbHIV-1testingconsistsofinitialscreeningwithanenzyme-linkedimmunosorbentassay(ELISA)todetectantibodiestoHIV-1.SpecimenswithareactiveELISAresultareretestedinduplicateIftheresultofeitherduplicatetestisreactive,doconfirmatorytesting：

Westernblot52第52页Althoughmuchlesscommonlyavailable,nucleicacidtesting(e.g.,viralRNAorproviralDNAamplificationmethod)canalsohelpdiagnosisincertainsituations.53第53页Preventionandtreatment54第54页PreventionNovaccineavailableBestpreventionistoavoidexposuretoth