HIV英文專業(yè)知識講座

Retroviruses1第1頁P(yáng)ropertiessharingwithRetroviridae

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

and1984NamedasHIVin19868第8頁Fran?oiseBarré-SinoussiLucMontagnier

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

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

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

chemokinereceptorfoundonlymphocytesandmonocytes.

Gp120:GP120bindstotheCD4receptorthenthechemokineco-receptorontheTcell.20第20頁gp12021第21頁Step2FusionanduncoatingHIVtransmembraneprotein(gp41)undergoesachangeallowingittobindtotheCCR5co-receptorGp41injectsthefusionpeptideintothecellmembraneFusionofHIVandcellularmembranesReleaseofnucleocapsidtocytoplasm22第22頁23第23頁P(yáng)arentalRNA

RNA/DNAHybrid

LinearDNA/DNAduplexCircularDuplexDNA

Integration Replication(DNAgenomeincell)Transcription ViralRNAgenome mRNA protein

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

incorporatedintheelongatingDNAchainformedfromthegenomicRNA,andterminatetheelongation(chainterminators)26第26頁ReverseTranscriptaseInhibitorsB.Nonnucleosidereversetranscriptaseinhibitors(NNRTIs):bindintoapocketwithinasubunitoftheenzyme,changingtheconformationoftheRTandinhibitingitsactivity27第27頁28第28頁IntegraseInhibitorRaltegravirwasrecentlyapproved,highlyeffectiveandwelltolerated29第29頁Step5ProviraltranscriptionProvirusmRNAStep6TranslationmRNAprotein30第30頁HIVProtease31第31頁Step8Assembly,maturationandrelease32第32頁P(yáng)athogenesisandimmunity33第33頁HowHIVcanbetransmittedSex:

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

Duringpregnancyorbirthandthroughbreastfeeding34第34頁HowHIVcanNOTbetransmittedThroughairorbycoughingandsneezingThroughfoodorirrigateThroughsweatandtearsBysharingcups,plates,andutensilswithaninfectedpersonBytouching,huggingandkissinganinfectedpersonBysharingclothesorshakinghandswithaninfectedpersonBysharingtoiletsandbathroomswithaninfectedpersonBylivingwithaninfectedpersonBymosquitoes,fleas,orotherinsects35第35頁TargetcellsHIVcaninfectavarietyofimmunecells:CD4+Tcells,macrophages,dentridiccellsmicroglialcells（小膠質(zhì)細(xì)胞）.36第36頁FromHIVInfectiontoAIDS37第37頁InfectionwithHIV-1isassociatedwithaprogressivedecreaseoftheCD4+Tcellcountandanincreaseinviralload.38第38頁CD4+Tcellcount(cellsperμL)

HIVRNAcopiesper

mLofplasma39第39頁StagesofHIVinfectionPrimaryinfectionAsymptomaticinfectionAIDS40第40頁P(yáng)rimaryinfectionInitialincubationperiod:

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

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

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

oralcandidiasis(thrush)鵝口瘡PneumocystiscariniipneumoniaTuberculosisHerpesvirusinfectionsEtc.46第46頁oralcandidiasis(thrush)47第47頁P(yáng)neumocystiscarinii

pneumonia(interstitialpneumonia)

Pneumocystiscarinii

48第48頁AIDS-associatedcancers:

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

Sarcoma

（多發(fā)性特發(fā)性出血性肉瘤）

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

Westernblot52第52頁Althoughmuchlesscommonlyavailable,nucleicacidtesting(e.g.,viralRNAorproviralDNAamplificationmethod)canalsohelpdiagnosisincertainsituations.53第53頁P(yáng)reventionandtreatment54第54頁P(yáng)reventionNovaccineavailableBestpreventionistoavoidexposuretoth