傳染病學Chapter32 反轉(zhuǎn)錄病毒

Chapter32Retrovirus

Retroviridaeinclude7genera:AlpharetrovirusBetaretrovirusGammaretrovirusDeltaretrovirus:

HTLV(HumanTLymphotropicVirus)EpsilonretrovirusLentivirus:

HIV(HumanimmunodeficiencyVirus)Spumavirus:

Section1Humanimmunodeficiencyvirus

(HIV)Ihaveit!–ithappenedonFriday,4February1983,at5:45p.m.

WorldAIDSprevalence2008

AIDSprevalenceinChina2006

HIV

PathogenofAIDS(AcquiredImmunodeficiencySyndrome).HIV-1isfoundworldwide,HIV-2isfoundprimarilyinWestAfrica.9Ⅰ.Biologicalproperties1.

Morphology:

Spherical,enveloped,spikes.2.Structure:

Core:2copiesof+ssRNA(dimmer);

reversetranscriptase;

integrase,protease,RNaseHCapsidprotein:P24Matrixprotein:P17Envelope:gp41,gp1201011gp41:

mediatesfusionoftheviralenvelopewiththecellmembrane,facilitatestheviriontoenterthecell.gp120:

*

beassociatedwithadsorption(bindingsiteforCD4moleculeofTcells).*beabletostimulatetheproductionofneutralizingantibodies.*easyvariation.123.Genes:StructuralgenesRegulatorygenesLTRStructuralgenes:

gag:

codingforcapsidproteins(p17,p24,p7)

pol:

codingforprotease,reversetranscriptaseetc.

env:

codingforgp120,gp41.134.Resistance:weak,100℃20mininactivatedfrozenblood68℃72h5.Replication:Adsorption:

gp120bindstoCD4moleculeofTcells

thenecessaryco-receptors

forHIV-1entry:

CXCR4

forT-cellline(T)-tropicstrains

CCR5

formacrophage(M)-tropicstrains14Penetration:

membranefusionUncoating:Biosythesis:

RNA---cDNA---RNA:DNAhybridmolecule---dsDNA---integratedintohostDNA(provirus)---staylatent---enteraproductivecycleAssembly,maturationandrelease:

budding1516Ⅱ.Pathogenesis&immunity1.Infectioussource:

patients(symptomatic),infectiouspeople(anti-HIV(+),asymptomatic).2.Transmissionpathway:

1)BySexualcontact;2)Bybloodorbloodproducts;3)Verticaltransmission:frommothertochild.173.Pathogenesis:gp120ofHIVselectCD4moleculeofTcells---virusesmultiplyinTcells---cell-mediatedimmunodeficiency---opportunisticinfectionsandtumorsformation---death18①

Viralreplicationinhibitscellbiosynthesis②Syncytiumformationviamembranegp120bindingtocellCD4antigen③CytotoxicTcelllysisofinfectedTcells④Induceappoptosis⑤

Naturalkillercells⑥Antibody-dependentcellcytotoxicity

⑦InducingautoantibodyDestructionofTcellsisachievedby:19DecreasedproductionofTcells

HIVinfectsthymocytesandbonemarrowhemopoieticstemcellsDamageofTcellfunction

Th1/Th2unbalancememoryCD4+TcellsMononuclearphagocyte

reservoirandvector204.ClinicalfeaturesExposure---Seroconversion---Asymptomatic—PGL(persistentgeneralizedlymphadenopath)

orARC(AIDS-relatedcomplex)---AIDS

a.OpportunisticInfections:

Protozoal,Fungal,Bacterial,Viral

b.OpportunisticTumours

Kaposi'ssarcomaisobservedin20%ofpatientswithAIDS.21艾滋病病人與卡波氏肉瘤22Ⅲ.DiagnosisThedetectionoftheantibodyagainstHIV

ThepresumptivediagnosisofHIVinfectionismadebythedetectionofantibodiesbyELISA.Thedefinitivediagnosisismadebywesternblot.

2.Thedetectionofviralcomponents(p24)ordetectionofviralRNA3.Isolationofthevirusinculture23Till2014FebruaryLivingHIVcarrierandAIDSpatients448,226

LivingAIDSpatients154,000Newinfection104,000Death138,95624Ⅳ.Preventionandtreatment

(1)Nucleoside

analoguesreversetranscriptase

inhibitors.AZT,DDC,DDIandlamuvidine.(2)Non-nucleoside

analoguereverse

transcriptaseinhibitorse.g.Nevirapine(抑制DNA合成)(3)Proteaseinhibitor