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Intranuclear HSV-1 DNA ejection induces major mechanical transformations suggesting mechanoprotection of nucleus integrity

Evilevitch, Alex LU orcid and Hohlbauch, Sophia V. (2022) In Proceedings of the National Academy of Sciences of the United States of America 119(9). p.1-12
Abstract

Maintaining nuclear integrity is essential to cell survival when exposed to mechanical stress. Herpesviruses, like most DNA and some RNA viruses, put strain on the nuclear envelope as hundreds of viral DNA genomes replicate and viral capsids assemble. It remained unknown, however, how nuclear mechanics is affected at the initial stage of herpesvirus infection—immediately after viral genomes are ejected into the nuclear space—and how nucleus integrity is maintained despite an increased strain on the nuclear envelope. With an atomic force microscopy force volume mapping approach on cell-free reconstituted nuclei with docked herpes simplex type 1 (HSV-1) capsids, we explored the mechanical response of the nuclear lamina and the chromatin... (More)

Maintaining nuclear integrity is essential to cell survival when exposed to mechanical stress. Herpesviruses, like most DNA and some RNA viruses, put strain on the nuclear envelope as hundreds of viral DNA genomes replicate and viral capsids assemble. It remained unknown, however, how nuclear mechanics is affected at the initial stage of herpesvirus infection—immediately after viral genomes are ejected into the nuclear space—and how nucleus integrity is maintained despite an increased strain on the nuclear envelope. With an atomic force microscopy force volume mapping approach on cell-free reconstituted nuclei with docked herpes simplex type 1 (HSV-1) capsids, we explored the mechanical response of the nuclear lamina and the chromatin to intranuclear HSV-1 DNA ejection into an intact nucleus. We discovered that chromatin stiffness, measured as Young’s modulus, is increased by ∼14 times, while nuclear lamina underwent softening. Those transformations could be associated with a mechanism of mechanoprotection of nucleus integrity facilitating HSV-1 viral genome replication. Indeed, stiffening of chromatin, which is tethered to the lamina meshwork, helps to maintain nuclear morphology. At the same time, increased lamina elasticity, reflected by nucleus softening, acts as a “shock absorber,” dissipating the internal mechanical stress on the nuclear membrane (located on top of the lamina wall) and preventing its rupture.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atomic force microscopy, Capsid, DNA ejection, Herpesvirus, Nucleus mechanics
in
Proceedings of the National Academy of Sciences of the United States of America
volume
119
issue
9
article number
e2114121119
pages
1 - 12
publisher
National Academy of Sciences
external identifiers
  • scopus:85125155796
  • pmid:35197285
ISSN
0027-8424
DOI
10.1073/pnas.2114121119
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2022 National Academy of Sciences. All rights reserved.
id
81e56739-dc76-4b2e-b820-96595ec3e1bd
date added to LUP
2022-03-17 12:23:18
date last changed
2024-06-14 14:14:57
@article{81e56739-dc76-4b2e-b820-96595ec3e1bd,
  abstract     = {{<p>Maintaining nuclear integrity is essential to cell survival when exposed to mechanical stress. Herpesviruses, like most DNA and some RNA viruses, put strain on the nuclear envelope as hundreds of viral DNA genomes replicate and viral capsids assemble. It remained unknown, however, how nuclear mechanics is affected at the initial stage of herpesvirus infection—immediately after viral genomes are ejected into the nuclear space—and how nucleus integrity is maintained despite an increased strain on the nuclear envelope. With an atomic force microscopy force volume mapping approach on cell-free reconstituted nuclei with docked herpes simplex type 1 (HSV-1) capsids, we explored the mechanical response of the nuclear lamina and the chromatin to intranuclear HSV-1 DNA ejection into an intact nucleus. We discovered that chromatin stiffness, measured as Young’s modulus, is increased by ∼14 times, while nuclear lamina underwent softening. Those transformations could be associated with a mechanism of mechanoprotection of nucleus integrity facilitating HSV-1 viral genome replication. Indeed, stiffening of chromatin, which is tethered to the lamina meshwork, helps to maintain nuclear morphology. At the same time, increased lamina elasticity, reflected by nucleus softening, acts as a “shock absorber,” dissipating the internal mechanical stress on the nuclear membrane (located on top of the lamina wall) and preventing its rupture.</p>}},
  author       = {{Evilevitch, Alex and Hohlbauch, Sophia V.}},
  issn         = {{0027-8424}},
  keywords     = {{Atomic force microscopy; Capsid; DNA ejection; Herpesvirus; Nucleus mechanics}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1--12}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences of the United States of America}},
  title        = {{Intranuclear HSV-1 DNA ejection induces major mechanical transformations suggesting mechanoprotection of nucleus integrity}},
  url          = {{http://dx.doi.org/10.1073/pnas.2114121119}},
  doi          = {{10.1073/pnas.2114121119}},
  volume       = {{119}},
  year         = {{2022}},
}