title: Parvovirus induced alterations in nuclear architecture and dynamics.
abstract: The nucleus of interphase eukaryotic cell is a highly compartmentalized structure containing the three-dimensional network of chromatin and numerous proteinaceous subcompartments. DNA viruses induce profound changes in the intranuclear structures of their host cells. We are applying a combination of confocal imaging including photobleaching microscopy and 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) studies revealed the homogeneity of this compartment. Markedly, in spite of increase in viral DNA content of the nucleus, a significant increase in the protein mobility was observed in infected compared to non-infected cells. Moreover, analysis of the dynamics of photoactivable capsid protein demonstrated rapid intranuclear dynamics of viral capsids. Finally, quantitative FRAP and cellular modelling were used to determine the duration of viral genome replication. Altogether, our findings indicate that parvoviruses modify the nuclear structure and dynamics extensively. Intranuclear crowding of viral components leads to enlargement of the interchromosomal domain and to chromatin marginalization via depletion attraction. In conclusion, parvoviruses provide a useful model system for understanding the mechanisms of virus-induced intranuclear modifications.
authors.affiliation: NanoScience Center, Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Teemu O
authors.initials: TO
authors.lastname: Ihalainen
authors.forename: Einari A
authors.initials: EA
authors.lastname: Niskanen
authors.forename: Juulia
authors.initials: J
authors.lastname: Jylhävä
authors.forename: Outi
authors.initials: O
authors.lastname: Paloheimo
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dross
authors.forename: Hanna
authors.initials: H
authors.lastname: Smolander
authors.forename: Jörg
authors.initials: J
authors.lastname: Langowski
authors.forename: Jussi
authors.initials: J
authors.lastname: Timonen
authors.forename: Maija
authors.initials: M
authors.lastname: Vihinen-Ranta
mesh_terms: D000818:Animals; D002415:Cats; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D036681:Fluorescence Recovery After Photobleaching; D016679:Genome, Viral; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism; D018613:Microscopy, Confocal; D010322:Parvoviridae Infections / Q000378:metabolism* / Q000821:virology; D017992:Parvovirus / Q000378:metabolism*; D017993:Parvovirus, Canine / Q000378:metabolism
chemical_list: D002843:Chromatin; D003911:Dextrans; D049452:Green Fluorescent Proteins