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1、BIOCHEMICALASPECTSOFCORONAVIRUSREPLICATIONLuisEnjuanes,FernandoAlmazn,IsabelSola,SoniaZúñiga,áEnriqueAlvarez,JuanReguera,andCarmenCapiscol*1.INTRODUCTIONExtensivemorphologicalandbiochemicalchangesoccurincoronavirus(CoV)-infectedcells.Nevertheless,thereisalimitedknowle
2、dgeofthebiochemicaleventsoccurringinhostcellsandinthebiochemistryoftheinfection.InfectionsbyCoVscausealterationsinhostcellsintranscriptionandtranslationpatterns,inthecellcycle,inthecytoskeleton,andinapoptosispathways.Inaddition,inthehost,CoVinfectionmaycauseinflammati
3、on,alterationsoftheimmuneresponse,ofcytokineandchemokinelevels,ofinterferon(INF)-inducedgeneexpressionandofstressresponses,andmodificationofcoagulationpathways.ThischapterwillfocusonselectedbiochemicalaspectsofCoVreplicationandtranscriptionwithspecialattentiontotheint
4、eractionbetweencellandviralfactors.2.INFLUENCEOFVIRALANDCELLULARPROTEINSINCoVREPLICATION2.1.NuclearLocalizationofCoVProteinsThereareatleastthreeCoVproteinsthathavebeenlocalizedwithinthenucleusofinfectedcells:nucleoprotein(N),3b,andnsp1(Table1).Thenucleolushasbeenimpli
5、catedinmanyaspectsofcellbiologythatincludefunctionssuchasribosomalrRNAsynthesisandribosomebiogenesis,genesilencing,senescence,andcellcycle1-5regulation.Thenucleoluscontainsdifferentfactorsincludingnucleolin,fibrillarin,spectrin,B23,rRNA,andribosomalproteinsS5andL9.Vir
6、usesinteractwiththenucleolusanditsantigens;viralproteinsco-localizewithfactorssuchasnucleolin,B23,2andfibrillarinandcausetheirredistributionduringinfection.NproteinsfromCoVgenusα*CentroNacionaldeBiotecnología,CSIC,Darwin,3,Cantoblanco,28049Madrid,Spain.1314L.ENJUANESE
7、TAL.Table1.NiVproteinsinthenucleusofinfectedcells.PROTEINVIRUSREFERENCENIBVChen,etal.,2003MHVWurm,etal.,2001SARS-CoVTimani,etal.,2004TGEVWurm,etal.,2001PRRSVRowland,etal.,1999EAVTijms,etal.,20023bSARS-CoVYuan,etal.,2005nsp1EAVvandeMeer,etal.,19996(transmissiblegastroe
8、nteritisvirus,TGEV),b(mousehepatitisvirus,MHV,andsevere6-8andacuterespiratorysyndromecoronavirus,SARS-CoV),andg(infectiousbr