病毒学英文版经典课件Virology-To Students

1VIROLOGYYingchunHou,M.D.,Ph.D.SchoolofLifeSciencesShaanxiNormalUniversity2IntroducingMyselfUniversityStudent:Xi’anMedicalCollegeMasterDegree:KunmingMedicalCollegeBasicMedicalTeacher:FMMUPh.D.Degree:FMMUPhysician(InternalMedicine)inXi-JingHospitalResearchAssociate:WayneStateUniversityPostdoctoralScholar:NIHPostdoctoralResearchFellow:WayneStateUniversitySeniorScientist:VAMedicalCenter,Detroit,MIProfessor:SNNU3Chapter1:VirusandVirologyVirus:Virusesbelongtomicroorganism,buttheyarethemostsimplebiologicalorganismintheworldthatcontainDNAorRNAcoreandproteincoatorcapsidonly(Virion).Virusesaresosmallthatyoucanseethemunderapowerfulmicroscopeorelectromicroscopeonly.Thelifecycleofvirusesisverysimplethatshowsvirusreplicationonly.Allofvirusmustsurviveincells.4Mostofvirusesareveryharmfultohumanbeing,animal,orplants.Noanyantibioticissensitivetovirussofar.So,virusdiseasesaremorethreatenedthanothermicro-organismstohumanhealth.Pseudovirus:Some“virus”containsDNAorRNAinside,buttheDNAorRNAisfromhost.Pseudoviruscannotbereplicated,anditisnotpathogenalso.ReversetranscriptvirusorDNAprovirus:SomeRNAviruscanbereverselytranscribedascDNA,andthecDNAcancombineintothegenomeofhost.Viroid:Nocoatorcapsid,so,thenucleicacidisnude.Viroidisthepathogentoplantsusually.Phage:Thevirusparasitesinbacteriaonly.5VirologyandItsImportancetoUsVirology:Aacademicfieldthatincludestheresearchesonvirusandcontrolthevirustoprotecthumanbeingandplant.Sometimeandforsomevirus,wecanusethevirustomakeresearches.Therolesofvirusestothedevelopmentoflifesciences:Virusdiseases,cardiovasculardiseases,andcancersarethemainkillerstomodernhumanbeing.Exceptingthat,virologyisveryimportantforthedevelopmentoflifesciencesasthefollows:6TheRoleofAnimalVirusesinUnderstandingtheBasicOutlinesofEukaryoticGeneRegulation:Thefirsttranscriptionalenhancerelement(actsinanorientation-anddistance-independentfashion)wasdescribedintheSV40genome,aswasadistance-andorientation-dependentpromoterelementobservedwiththesamevirus.Thetranscriptionfactorsthatbindtothepromoter,SP-1,ortotheenhancerelement,suchasAP-1,AP-2,andwhichareessentialtopromotetranscriptionalongwiththebasalfactors,werefirstdescribedwithSV40.AlmosteverythingweknowaboutthestepsofmessengerRNA(mRNA)processingbeganwithobservationsmadewithviruses.Forexamples,RNAsplicingofnewtranscriptswasfirstdescribedwiththeadenoviruses.ThesignalforpolyadenylationinthemRNAwasfirstfoundusingSV40.7Thecapandmethylationofbasesatthe5'endofmRNAwasfirstdetectedusingreoviruses.Thediscoveryoftheroleofinterferonininducingasetofgeneproductsthatactontranslationalregulatoryeventsowesitsoriginstovirology.Posttranslationalprocessingofproteinsbyproteases,carbohydrateadditiontoproteinsintheGolgiapparatus,phosphorylationbyawidevarietyofimportantcellularproteinkinases,ortheadditionoffattyacidstomembrane-associatedproteinshaveallbeenprofitablystudiedusingviruses.Indeed,agooddealofourpresent-dayknowledgeincellbiologyofhowproteintraffickingoccursandisregulatedincellscomesfromtheuseofvirus-infectedcellsystems.Clearly,thefieldofgeneregulationhasreliedonvirologyformanyofitscentraltenets.8TheRoleofAnimalVirusesintheRecombinantDNARevolution:Thediscoveryoftheenzymereversetranscriptaseinretroviruses(5,138)notonlyhelpedtoprovehowretrovirusesreplicatebutalsoprovidedanessentialtooltoproducecomplementaryDNAs(cDNAs).Thefirstrestrictionenzymemapofachromosome,HindIIplusIII,waswithSV40DNA,andthefirstDNAtoshowthespecificityofarestrictionenzymewasSV40DNAwithEcoRI.SomeoftheearliestDNAcloningexperimentsusedSV40DNAintolambda,orhumanb-hemoglobingenesintoSV40DNA,toconstructthefirstmammalianexpressionvectors.Indeed,adebateabouttheseveryexperimentsledtoatemporarymoratoriumonallsuchrecombinantexperiments.9Fromthebeginning,severalanimalviruseshadbeendevelopedintoexpressionvectorsforforeigngenes,includingSV40,theretroviruses,theadenoviruses,andadeno-associatedvirus,whichhastheremarkablepropertyofsitepreferentialintegration.Moderndaystrategiesofgenetherapywillsurelyrelyonsomeoftheserecombinantviruses.ThefirstcDNAcloningofhemoglobinsequencesutilizedlambdavectorsforthecloningandreplicationofthesemRNAcopies.Inanicetwistofevents,thelong-elusivehepatitisvirusC(non-A,non-B)wasclonedfromserumusingrecombinantDNAtechniques,reversetranscriptase,andlambdaphagevectors.10TheRoleofAnimalVirologyinOncology:Itisnottoostrongastatementtosaythatweoweagreatproportionofourpresentunderstandingoftheoriginsofhumancancerstotwomajorgroupsofanimalviruses,theretrovirusesandDNAtumorviruses.TheoncogeneswerefirstdiscoveredandproventoexistinavirusandtheninthehostcellgenomeusingRoussarcomavirus.Awidevarietyofretroviruseshavecaptured,altered,anddeliveredoncogenestothevirologists.Theinsertionofretrovirusesintothegenomesofcancerouscellsalsohelpedtolocateadditionaloncogenes.Thesecondgroupofgenesthatcontributetotheoriginsofhumancancers,thetumorsuppressorgenes,hasbeenshowntobeintimatelyassociatedwiththeDNAtumorviruses.11Geneticalterationsatthep53locusarethesinglemostcommonmutationsknowntooccurinhumancancers(60%to65%ofthetime).Thep53proteinw