title: Remodeling nuclear architecture allows efficient transport of herpesvirus capsids by diffusion.
abstract: The nuclear chromatin structure confines the movement of large macromolecular complexes to interchromatin corrals. Herpesvirus capsids of approximately 125 nm assemble in the nucleoplasm and must reach the nuclear membranes for egress. Previous studies concluded that nuclear herpesvirus capsid motility is active, directed, and based on nuclear filamentous actin, suggesting that large nuclear complexes need metabolic energy to escape nuclear entrapment. However, this hypothesis has recently been challenged. Commonly used microscopy techniques do not allow the imaging of rapid nuclear particle motility with sufficient spatiotemporal resolution. Here, we use a rotating, oblique light sheet, which we dubbed a ring-sheet, to image and track viral capsids with high temporal and spatial resolution. We do not find any evidence for directed transport. Instead, infection with different herpesviruses induced an enlargement of interchromatin domains and allowed particles to diffuse unrestricted over longer distances, thereby facilitating nuclear egress for a larger fraction of capsids.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544; Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544;
authors.forename: Jens B
authors.identifier: http://orcid.org/0000-0001-7252-5541
authors.initials: JB
authors.lastname: Bosse
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544; Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544;
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hogue
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544;
authors.forename: Marina
authors.initials: M
authors.lastname: Feric
authors.affiliation: Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544;
authors.forename: Stephan Y
authors.initials: SY
authors.lastname: Thiberge
authors.affiliation: Institute of Virology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Sodeik
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544;
authors.forename: Clifford P
authors.initials: CP
authors.lastname: Brangwynne
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544; Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544; lenquist@princeton.edu.
authors.forename: Lynn W
authors.initials: LW
authors.lastname: Enquist
mesh_terms: D002213:Capsid / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004058:Diffusion; D006564:Herpesviridae / Q000378:metabolism* / Q000502:physiology; D008856:Microscopy, Fluorescence; D021381:Protein Transport; D014779:Virus Replication
keywords: capsid; herpes; light sheet; nucleus; ring sheet