González-Almela, EstherCastells García, Àlvaro, 1991-Le Dily, FrançoisFernández Merino, ManuelCarnevali, DavideCuscó Pons, Pol, 1987-Di Croce, LucianoCosma, Maria Pia2025-09-092025-09-092025González-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/s41467-025-60534-62041-1723http://hdl.handle.net/10230/71155Herpes 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.application/pdfeng© 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/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-025-60534-6ChromatinNuclear organizationSingle-molecule biophysicsinfo:eu-repo/semantics/openAccess