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

González-Almela, Esther; Castells García, Àlvaro, 1991-; Le Dily, François; Fernández Merino, Manuel; Carnevali, Davide; Cuscó Pons, Pol, 1987-; Di Croce, Luciano; Cosma, Maria Pia

doi:http://dx.doi.org/10.1038/s41467-025-60534-6

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

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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

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.