ViralGenomeandStructuresLaboratoryofMedicalMolecularVirologyChangLiuhttp://v.163.com/special/opencourse/virology.htmlBreakthroughin1950’s•Theviralnucleicacidgenomecarriestheinformationneededtoreplicate,build,andspreadvirionsintheworld.•OneofthebuildingblocksofMolecularBiology•T4,TMVHershey-ChoseexperimentwithphageT4Fraenkel-Conrat’sworkwithTMVSevenGenomeTypes•EitherDNAorRNA•Structurallydiverse:linear,circular,segmented,gapped,single-stranded(+)strand,single-stranded(-)strand,singlestranded(ambisense),double-stranded,somehavecovalentlyattachedproteins,somehavecross-linkedendsofdouble-strandedDNA•RNAWorldhypothesisWhatinformationisencodedinaviralgenome？•Replicationofviralgenome•Assemblyandpackagingofthegenome•Regulationandtimingofthereplicationcycle•Modulationofhostdefenses•SpreadtoothercellsandhostsInformationNotcontainedinviralgenomes•Nogenesencodingthecompleteproteinsynthesismachinery•Nogenesencodingproteininvolvedinenergyproductionormembranebiosynthesis•NoclassicalcentromeresortelomeresfoundinstandardhostchromosomesTheBaltimoreSystem•ViralgenomemustmakemRNAthatcanbereadbyhostribosomes•NOTall(+)RNAismRNA•Eachwayhasuniquepolymerase,primer,templateandterminationrequirements•EachvirusfamilyhasitsowncharacteristicgenomestrategySevenclassesdistinguishedbygenomereplicationstrategiesdsDNA,ssDNAdsRNA,+ssRNA,-ssRNA,RetrodsDNAgenomes•TheproblemofreplicatingtheendsoflinearDNAmoleculesthroughtheuseofRNAprimers.CirculardsDNAgenomesthatarereplicatedinthenucleusLineardsDNAgenomesthatarereplicatedinthenucleusLineardsDNAgenomesthatarereplicatedinthenucleusdsDNAgenomesthatarereplicatedinthecytoplasmssDNAgenomesAbasicproblemwithassDNAgenome:•RNAcanonlybemadefromadsDNAtemplate,–ssDNAmustbeconvertedintodsDNAbeforemRNAismade–DNAsynthesismustprecedemRNAproductionLinearssDNAgenomesthatarereplicatedinthenucleusRNAgenomes•CellshaveNORNA-dependentRNApolymerases(RdRp)toreplicatethegenomesofRNAviruses,ortomakemRNAfromRNA•RNAvirusgenomesencodenovelRdRp•PolymerasesproducebothRNAgenomesandmRNAfromRNAtemplates•+ssRNA,-ssRNA,dsRNA+ssRNA•HepatitisAvirus,footandmouthdiseasevirus,andrhinoviruseswhichcausethecommoncold.•ThecoronaviruseswhichincludesimportantveterinaryvirusesandtheSARSvirus.•HepatitisCvirus.•Yellowfevervirus.Positive-strandRNAvirusesthatmakenosubgenomicmRNAsPositive-strandRNAvirusesthatmakeoneormoresubgenomicmRNAs-ssRNA•RdRp•Reassortment:InfluenzavirusNegative-strandRNAviruseAmbisenseRNAviruseDouble-strandedRNA(dsRNA)•ManydsRNAgenomesaresegmented•dsRNAcannotbetranslatedbyribosomesdsRNAvirusesRetrovirus•HIV•HTLV•IntegrateintothehostDNA•HBVRetrovirusesHepadnavirusesStructure•Nanometer:10^-9meters•Atom:0.2-0.3nmdiameter•Alphahelixinprotein:1nmdiameter•DNA:2nmdiameter•Ribosome:20nmdiameter•Poliovirus:30nm•Mimivirus:750nmFunctionsofvirionproteins•Protectionofthegenome–Assemblyofastable,protectiveproteinshell–Specificrecognitionandpackagingofthenucleicacidgenome–Interactionwithhostcellmembranestoformtheenvelope•Deliveryofthegenome–Bindingtohostcellreceptors–Transmissionofsignalsthatinduceuncoatingofthegenome–Inductionoffusionwithhostcellmembranes–Interactionwithcellcomponentstodirecttransportofgenometotheappropriatesit•Otherinteractionswithhost–Withcellcomponentstoensureefficientinfectiouscycle–Withcellcomponentsfortransporttositesofasse...
