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IPS,CAS-20061VIROLOGYCOURSE#1Generalvirology,History,Taxonomy,TechniquesinvirologyIPS,CAS-20062Welcometomyworld!IPS,CAS-20063•Virus:anoncellulargeneticelementthatinfectsacellforitsownreplication,ithasanextracellularstate.•Avirusparticlecontainingnucleicacidsurroundedbyproteinandothermacromolecularcomponentsiscalledvirion.•Viruseshaveaheavydependenceonhost-cellstructuralandmetaboliccomponents.•Virusescanconferimportantnewpropertiesontheirhostcell.•Virusesmaybenonproductive,latent,oncogenic,chronicorlytic.DefinitionIPS,CAS-20064I.GENERALVIROLOGY1840’s:Agentsnotvisibleundermicroscope1880-1900:LouisPasteur:Absenceofspontaneousgeneration•AdolfMayerandDimitryIvanovsky:Tobaccomosaic-Transmissionofagentbythejuiceofsickplantstohealthyplants-Notretainedbyporousglassfilters(CharlesChamberland)-ButRobertKoch’spostulatenotvalid•MartinusBeijerinck:Conceptoffilterableagentcalledvirus(poison)notreplicatingoutsidehostbutamplifiedinhost(contagiouslivingliquid).TMV,FMDV,YFVConceptofvirology.HistoryIPS,CAS-20065Koch’spostulate:-Agentregularlyfoundinthelesionofthedisease-organismmustbeisolatedinpureculture-inoculationofsuchculturetohostshouldinitiatethedisease-theorganismshouldagainbeisolatedfromthelesionsofthehostIPS,CAS-200661900-1910:NewconseptsVirusescanbetransmittedbymosquitoes1901Virusescancausecancer(Leukemia,Sarcoma)1908-1911Virusesshowlesionsinsidecells(Negricorpus1903)1930-1955:1.Virusescontainproteinsthatcanbe:•precipitated,•concentrated,•Inactivated(resistancetophysicalandchemicalagents),•neutralized(productionofantibodiesinanimals),•electrophoresed2.Virusescontainphosphorus3.Virusescontainribonucleicacidsordeoxyribonucleicacids1917:VirustitrationplaqueassayIPS,CAS-200674.Electronmicroscopy(1937)5.Viruseshavedifferentstructures6.Theuseofanimalsforviruscultivation(1931)Mouse(leukemialymphoidvirus)Embryonatedeggs(poxvirus)7.Theuseofcellcultureforviruscultivation(1948)PoliovirusVaccinedevelopmentinanimals(rabies,YFV)embryonatedchickeneggs(YFV,smallpox,influenza)cellculture(poliovirus)IPS,CAS-200681960now:Cellbiology:eukaryotictranscriptionmachineryandgeneregulation(transcriptionfactors,polymerasepromoters,RNAsplicing,mRNApolyadenylation,cappingandmethylation,RNAtransportfromthenucleustocytoplasm,regulationoftranslationandIRES,proteinprocessing,IFN-regulatedsignals…)1970now:MolecularbiologyandrecombinantDNA(Reversetranscriptase,Restrictionenzymemappingchart,LambdaphageforDNAlibrary,proteinexpressionvectors,siteintegrationinhostgenome,genetherapy…)RoleandbenefitofvirologyincellandmolecularbiologyIPS,CAS-20069DNAViruses:RNAViruses:AdenovirusesCoronavirusesIridovirusesFilovirusesHerpesvirusesOrthomyxovirusesPapovavirusesParamyxovirusesParvovirusesPicornavirusesPoxvirusesRetrovirusesViralHepatitisRhabdovirusesArbovirusesArenaviruses,Bunyaviruses,Flaviviruses,TogavirusesDiarrhoeaVirusesAstroviruses,Caliciviruses,Reoviruses(inc.Rotaviruses)•Taxonomicorder(Order,Family,Subfamily,Genus,Species,strain,variant)•Generalhostrange(bacteria,plant,animal;hostrange,pathogenesis,transmission,habitat…)•DiseaseorderII.VIRUSTAXONOMYIPS,CAS-200610(DNAvirusinChinese)://~dmsander/Big_Virology/BVFamilyGroup.html#IV://~dmsander/garryfavweb.htmlVirusclassificationICTV:-virus,-virinae,-viridae,-viralesCapitalizedanditalicized:ex:HRSVIPS,CAS-200611Mostfamilieshavedistinctvirionmorphology,genomestructure,andreplicationstrategyVIII.Subviralagents(Viroids,satellitesPrions)IXUnassignedvirusIPS,CAS-200612Hostrange:AlgaeArchealBacteriaFungiInvertebratePlantAnimalProtozoaVertebratesSomevirusescanreplicateindifferenttypesofhosts:ex:Flaviviruses,Bunyaviridae,andAlphaviridiaeIPS,CAS-200613VirusStructureVirusesconsistofnucleicacids,capsid,and/orenvelope.:20nmto300nm(Ebola:1000nmlong)Largestvirus:Smallpox(天花病毒)is200nmSmallestvirus:Poliovirus(脊髄灰质炎病毒)is28nmVirusgenome:Smallerthanthoseofcells,thelargestknownviralgenome:vaccinia(牛痘)isonly190KB.Bacterialgenomes:1000-9000KBIPS,CAS-200615VirusSymmetryHelicalsymmetry:Tobaccomosaicvirus(TMV).Icosahedron:Themostefficientarrangementforsubunitsinaclosedshell.Envelopedviruses:envelopeconsistsoflipidbilayerwithglycoproteinsembeddedinit.Virussymmetryreferstoitsnucleocapside.Complexviruses:T4bacteriophageIPS,CAS-200616VirusMorphologyIPS,CAS-200617Icosahedricsymetryofvirusesbycryo-electronmicroscopyT=3symetryIPS,CAS-200618III.VIRUSESANDDISEASESCancer:EpsteinBarr:Burkittlymphoma(1962-68)andmononucleosisHumanT-cellleukemia(1977-1980)Hepatocellularcarcinoma-HepatitisB(1967)PapillomavirusHepatitisC(1985):adifferentstoryfromRNAvirusAcutediseases:Ex:Influenza,dengueChronicdisease:Ex:Herpes,relapsingvirusesSymptomaticdiseases:AcuterespiratorydiseaseViralencephalitisHepatitisDiarrhea…IPS,CAS-200619IV.VIRUSLIFECYCLE1.Attachment(adsorpt