Parvovirus Induced Alterations in Nuclear Architecture and Dynamics 英文参考文献.docVIP

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Parvovirus Induced Alterations in Nuclear Architecture and Dynamics 英文参考文献.doc

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Parvovirus Induced Alterations in Nuclear Architecture and Dynamics 英文参考文献

ParvovirusInducedAlterationsinNuclearArchitecture andDynamics TeemuO.Ihalainen1,EinariA.Niskanen1,JuuliaJylha¨va¨1,2,OutiPaloheimo1,NicolasDross3 ,Hanna Smolander1,4,Jo¨rgLangowski3,JussiTimonen5,MaijaVihinen-Ranta1* 1NanoScienceCenter,DepartmentofBiologicalandEnvironmentalScience,UniversityofJyva¨skyla¨, Jyva¨skyla¨, Finland,2DepartmentofMicrobiologyandImmunology, Medical School, University of Tampere, Tampere, Finland, 3Division Biophysics of Macromolecules, German Cancer Research Center (DKFZ), Heidelberg, Germany, 4DepartmentofVirology,HaartmanInstitute,UniversityofHelsinki,Helsinki,Finland,5DepartmentofPhysics,UniversityofJyva¨skyla¨, Jyva¨skyla¨, Finland Abstract Thenucleusofinterphaseeukaryoticcellisahighlycompartmentalizedstructurecontainingthethree-dimensionalnetwork ofchromatin andnumerousproteinaceous subcompartments.DNA virusesinduce profound changes intheintranuclear structuresoftheirhostcells.Weareapplyingacombinationofconfocalimagingincludingphotobleachingmicroscopyand computational methods to analyze the modifications of nuclear architecture and dynamics in parvovirus infected cells. Upon canine parvovirus infection, expansion of the viral replication compartment is accompanied by chromatin marginalization to the vicinity of the nuclear membrane. Dextran microinjection and fluorescence recovery after photobleaching(FRAP)studiesrevealedthehomogeneityofthiscompartment.Markedly,inspiteofincreaseinviralDNA contentofthenucleus,asignificantincreaseintheproteinmobilitywasobservedininfectedcomparedtonon-infected cells.Moreover,analyzisofthedynamicsofphotoactivablecapsidproteindemonstratedrapidintranucleardynamicsofviral capsids.Finally,quantitativeFRAPandcellularmodellingwereusedtodeterminethedurationofviralgenomereplication. Altogether, our findings indicate that parvoviruses modify the nuclear structure and dynamics extensively. Intranuclear crowdingofviralcomponentsleadstoenlargementoftheinterchromosomaldomainandtochromatinmarginalizati