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

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 underg...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/71155
Acceso en línea:http://hdl.handle.net/10230/71155
http://dx.doi.org/10.1038/s41467-025-60534-6
Access Level:acceso abierto
Palabra clave:Chromatin
Nuclear organization
Single-molecule biophysics
Descripción
Sumario: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.