Reconstituted virus–nucleus system reveals mechanics of herpesvirus genome uncoating
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 i...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2022-01-01
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| Series: | QRB Discovery |
| Subjects: | |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2633289221000144/type/journal_article |
| _version_ | 1811155719983988736 |
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| author | Alex Evilevitch Efthymios Tsimtsirakis |
| author_facet | Alex Evilevitch Efthymios Tsimtsirakis |
| author_sort | Alex Evilevitch |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T04:38:14Z |
| format | Article |
| id | doaj.art-16a3b4abd7064ebbba994ab0dfea5a3a |
| institution | Directory Open Access Journal |
| issn | 2633-2892 |
| language | English |
| last_indexed | 2024-04-10T04:38:14Z |
| publishDate | 2022-01-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | QRB Discovery |
| spelling | doaj.art-16a3b4abd7064ebbba994ab0dfea5a3a2023-03-09T12:43:36ZengCambridge University PressQRB Discovery2633-28922022-01-01310.1017/qrd.2021.14Reconstituted virus–nucleus system reveals mechanics of herpesvirus genome uncoatingAlex Evilevitch0https://orcid.org/0000-0002-0245-9574Efthymios Tsimtsirakis1Department of Experimental Medical Science, Lund University, Lund, SwedenDepartment of Experimental Medical Science, Lund University, Lund, SwedenThe 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.https://www.cambridge.org/core/product/identifier/S2633289221000144/type/journal_articleAFMnucleuschromatinmechanicscapsidHerpes Simplex Virus type 1 |
| spellingShingle | Alex Evilevitch Efthymios Tsimtsirakis Reconstituted virus–nucleus system reveals mechanics of herpesvirus genome uncoating QRB Discovery AFM nucleus chromatin mechanics capsid Herpes Simplex Virus type 1 |
| title | Reconstituted virus–nucleus system reveals mechanics of herpesvirus genome uncoating |
| title_full | Reconstituted virus–nucleus system reveals mechanics of herpesvirus genome uncoating |
| title_fullStr | Reconstituted virus–nucleus system reveals mechanics of herpesvirus genome uncoating |
| title_full_unstemmed | Reconstituted virus–nucleus system reveals mechanics of herpesvirus genome uncoating |
| title_short | Reconstituted virus–nucleus system reveals mechanics of herpesvirus genome uncoating |
| title_sort | reconstituted virus nucleus system reveals mechanics of herpesvirus genome uncoating |
| topic | AFM nucleus chromatin mechanics capsid Herpes Simplex Virus type 1 |
| url | https://www.cambridge.org/core/product/identifier/S2633289221000144/type/journal_article |
| work_keys_str_mv | AT alexevilevitch reconstitutedvirusnucleussystemrevealsmechanicsofherpesvirusgenomeuncoating AT efthymiostsimtsirakis reconstitutedvirusnucleussystemrevealsmechanicsofherpesvirusgenomeuncoating |