Herpes simplex virus type 1 reshapes host chromatin architecture via transcription machinery hijacking

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  • dc.contributor.author González-Almela, Esther
  • dc.contributor.author Castells García, Àlvaro, 1991-
  • dc.contributor.author Le Dily, François
  • dc.contributor.author Fernández Merino, Manuel
  • dc.contributor.author Carnevali, Davide
  • dc.contributor.author Cuscó Pons, Pol, 1987-
  • dc.contributor.author Di Croce, Luciano
  • dc.contributor.author Cosma, Maria Pia
  • dc.date.accessioned 2025-09-09T06:01:19Z
  • dc.date.available 2025-09-09T06:01:19Z
  • dc.date.issued 2025
  • dc.description.abstract Herpes simplex virus type 1 (HSV-1) remodels the host chromatin structure and induces a host-to-virus transcriptional switch during lytic infection. We combine super-resolution imaging and chromosome-capture technologies to identify the mechanism of remodeling. We show that the host chromatin undergoes massive condensation caused by the hijacking of RNA polymerase II (RNAP II) and topoisomerase I (TOP1). In addition, HSV-1 infection results in the rearrangement of topologically associating domains and loops, although the A/B compartments are maintained in the host. The position of viral genomes and their association with RNAP II and cohesin is determined nanometrically. We reveal specific host-HSV-1 genome interactions and enrichment of upregulated human genes in the most contacting regions. Finally, TOP1 inhibition fully blocks HSV-1 infection, suggesting possible antiviral strategies. This viral mechanism of host chromatin rewiring sheds light on the role of transcription in chromatin architecture.
  • dc.description.sponsorship We acknowledge support from Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (2018GZR110103001 to M.P.C.); Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology (20200730009 to M.P.C.); National Natural Science Foundation of China (31971177 and 32270577 to M.P.C., 3221101299 to A.C.G.); Science and Technology Program of Guangzhou, China (202002030146 to M.P.C.); Guangdong Foreign Young Talent Program (WGZJXM04 to A.C.G.); Spanish Ministry of Science and Innovation (grant no. PID2020-114080GB I00/AEI/10.13039/501100011033 and grant no. BFU2017-86760-P/AEI/FEDER, UE to M.P.C.) and an AGAUR grant from the Department of Research and Universities of Generalitat de Catalunya (2021-SGR2021-01300 to M.P.C.); Spanish Ministry of Science and Innovation to the European Molecular Biology Laboratory (EMBL) partnership (to M.P.C.); the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN?AEI /10.13039/501100011033); European Social Fund (FI_B00103 to M.F.M.). Funding for open access charge: National Natural Science Foundation of China (NSFC) grant (3221101299 to A.C.G.).; Spanish Ministry of Economy, Industry and Competitiveness (PID2019-108322GB-100 to L.D.C.).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation González-Almela E, Castells-Garcia A, Le Dily F, Merino MF, Carnevali D, Cusco P, et al. Herpes simplex virus type 1 reshapes host chromatin architecture via transcription machinery hijacking. Nat Commun. 2025 Jun 19;16(1):5313. DOI: 10.1038/s41467-025-60534-6
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-025-60534-6
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/71155
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Commun. 2025 Jun 19;16(1):5313
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-114080GB I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-108322GB-100
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86760-P
  • dc.rights © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Chromatin
  • dc.subject.keyword Nuclear organization
  • dc.subject.keyword Single-molecule biophysics
  • dc.title Herpes simplex virus type 1 reshapes host chromatin architecture via transcription machinery hijacking
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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