Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 42, Pages E5725-E5733Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1513876112
Keywords
herpes; capsid; nucleus; ring sheet; light sheet
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Funding
- National Institutes of Health (NIH) [NS033506, NS060699]
- NSF CAREER [1253035]
- NIH [1DP2GM105437-01]
- Niedersachsen-Research Network on Neuroinfectiology of the Ministry of Science and Culture of Lower Saxony, Germany
- German Research Foundation [BO 4158/1-1]
- American Cancer Society [PF-13-050-01-MPC]
- Division Of Physics
- Direct For Mathematical & Physical Scien [1253035] Funding Source: National Science Foundation
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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.
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