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1、HumanPapillomaVirusBasicbiology,infection,andpsychologicaleffects.WhatisHPV?Papillomavirusesaresmall,approximately52-55nmindiameter.Theyarenon-enveloped,icosahedraparticles.Thisshapeismadeupof12pentamericand60hexamericcapsomersarrangedonaT=7lattice.Theircarpsidiscomposedoftwoproteins,amajor(L
2、1)andminor(L2).SEMimageofaHumanPapillomaVirusandacomputermodelshowingthestructureofthevirus.TheyareDNAviruses.HPVispartofthefamilyknownasPapovaviruses,whichwasnamedforit’sthreemainmembers:PApillomavirus,POlyomavirus,andsimianVacuolatingAgent.Theyarefoundinmanyvertebrates,andexhibithighspecies
3、specificity.Thisfamilycontainstwogeneraofoncogenicviruses,PapillomaandPolyomaviruses.ThePapillomavirus’genomeiscircular,d/sDNAapproximately8,000bpinsize.ManyoftheHPVgenomeshavebeensequencedandhaveageneticorganizationsimilartothatofHPV-16,oneoftheoncogenicstrains.HowDoesHPVWork?HPVinfectstheba
4、salcellsofthedermallayer,andearlygeneexpressionoccursinthesecells.LategeneexpressionandhighcopyDNAsynthesisoccursonlyinterminallydifferentiatedepidermalcells.Thisimpliesalinkbetweendifferentiationandgeneexpression,althoughthenatureofthislinkisunknown.SomestrainsofHPVareabletotransformhostcell
5、sontheirown,whereasothersrequirecofactors.ExpressionofthePapillomavirusgenomeisverycomplexandnotwellunderstood,becauseithasatleastsevenpromoters,exhibitsmanyalternativesplicingpatterns,andhasanunknownlinktocelldifferentiation.HPVInfectionOutcomesE6andE7interactwithmanycellularproteins,whichin
6、fluencetheoutcomeofinfection.HowDoesHPV“Cause”Cancer?Inhigh-riskHPVstrains16,18,31,39,45and59:ProteinE6interactswithp53inthehostcellandpromotesit’sdegradationviatheubiquitindependentpathway.ProteinE7complexeswithretinioblastomaprotein(Rb),therebyinactivatingit.Rbandp53arebothtumorsuppressors,
7、involvedinDNArepairandcelldeath.HPVandCervicalCancerIn1995astudybytheInternationalBiologicalStudyonCervicalCancermorethan1,000specimensofinvasivecervicalcancerweretestedforthepresenceofHPVviaapolymerasechainreaction-basedassayandfoundthat:HPV
