Reconstituted virus-nucleus system reveals mechanics of herpesvirus genome uncoating
Evilevitch, Alex LU
and Tsimtsirakis, Efthymios
LU
(2022)
In QRB Discovery
3.
- Abstract
The viral replication cycle is controlled by information transduced through both molecular and mechanical interactions. Viral infection mechanics remains largely unexplored, however, due to the complexity of cellular mechanical responses over the course of infection as well as a limited ability to isolate and probe these responses. Here, we develop an experimental system consisting of herpes simplex virus type 1 (HSV-1) capsids bound to isolated and reconstituted cell nuclei, which allows direct probing of capsid-nucleus mechanics with atomic force microscopy (AFM). Major mechanical transformations occur in the host nucleus when pressurised viral DNA ejects from HSV-1 capsids docked at the nuclear pore complexes (NPCs) on the nuclear... (More)
The viral replication cycle is controlled by information transduced through both molecular and mechanical interactions. Viral infection mechanics remains largely unexplored, however, due to the complexity of cellular mechanical responses over the course of infection as well as a limited ability to isolate and probe these responses. Here, we develop an experimental system consisting of herpes simplex virus type 1 (HSV-1) capsids bound to isolated and reconstituted cell nuclei, which allows direct probing of capsid-nucleus mechanics with atomic force microscopy (AFM). Major mechanical transformations occur in the host nucleus when pressurised viral DNA ejects from HSV-1 capsids docked at the nuclear pore complexes (NPCs) on the nuclear membrane. This leads to structural rearrangement of the host chromosome, affecting its compaction. This in turn regulates viral genome replication and transcription dynamics as well as the decision between a lytic or latent course of infection. AFM probing of our reconstituted capsid-nucleus system provides high-resolution topographical imaging of viral capsid docking at the NPCs as well as force volume mapping of the infected nucleus surface, reflecting mechanical transformations associated with chromatin compaction and stiffness of nuclear lamina (to which chromatin is tethered). This experimental system provides a novel platform for investigation of virus-host interaction mechanics during viral genome penetration into the nucleus.
(Less)
- author
- Evilevitch, Alex
LU
and Tsimtsirakis, Efthymios
LU
- organization
- publishing date
- 2022-12-20
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- AFM, capsid, chromatin, Herpes Simplex Virus type 1, mechanics, nucleus
- in
- QRB Discovery
- volume
- 3
- article number
- e2
- publisher
- Cambridge University Press
- external identifiers
-
- scopus:85121743909
- pmid:37529281
- ISSN
- 2633-2892
- DOI
- 10.1017/qrd.2021.14
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: ©
- id
- c4f221ad-3e9f-4205-ba53-9d81a41dc4cb
- date added to LUP
- 2022-03-17 12:23:39
- date last changed
- 2024-05-30 10:44:14
@article{c4f221ad-3e9f-4205-ba53-9d81a41dc4cb,
abstract = {{<p>The viral replication cycle is controlled by information transduced through both molecular and mechanical interactions. Viral infection mechanics remains largely unexplored, however, due to the complexity of cellular mechanical responses over the course of infection as well as a limited ability to isolate and probe these responses. Here, we develop an experimental system consisting of herpes simplex virus type 1 (HSV-1) capsids bound to isolated and reconstituted cell nuclei, which allows direct probing of capsid-nucleus mechanics with atomic force microscopy (AFM). Major mechanical transformations occur in the host nucleus when pressurised viral DNA ejects from HSV-1 capsids docked at the nuclear pore complexes (NPCs) on the nuclear membrane. This leads to structural rearrangement of the host chromosome, affecting its compaction. This in turn regulates viral genome replication and transcription dynamics as well as the decision between a lytic or latent course of infection. AFM probing of our reconstituted capsid-nucleus system provides high-resolution topographical imaging of viral capsid docking at the NPCs as well as force volume mapping of the infected nucleus surface, reflecting mechanical transformations associated with chromatin compaction and stiffness of nuclear lamina (to which chromatin is tethered). This experimental system provides a novel platform for investigation of virus-host interaction mechanics during viral genome penetration into the nucleus. </p>}},
author = {{Evilevitch, Alex and Tsimtsirakis, Efthymios}},
issn = {{2633-2892}},
keywords = {{AFM; capsid; chromatin; Herpes Simplex Virus type 1; mechanics; nucleus}},
language = {{eng}},
month = {{12}},
publisher = {{Cambridge University Press}},
series = {{QRB Discovery}},
title = {{Reconstituted virus-nucleus system reveals mechanics of herpesvirus genome uncoating}},
url = {{http://dx.doi.org/10.1017/qrd.2021.14}},
doi = {{10.1017/qrd.2021.14}},
volume = {{3}},
year = {{2022}},
}