Herpes simplex virus type 1 reshapes host chromatin architecture via transcription machinery hijacking
Esther González-Almela,
Alvaro Castells-Garcia,
François Dily,
Manuel Fernández Merino,
Davide Carnevali,
Pol Cusco,
Luciano Croce and
Maria Pia Cosma ()
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Esther González-Almela: Southern Medical University
Alvaro Castells-Garcia: Southern Medical University
François Dily: Centre for Genomic Regulation (CRG). The Barcelona Institute of Science and Technology
Manuel Fernández Merino: Centre for Genomic Regulation (CRG). The Barcelona Institute of Science and Technology
Davide Carnevali: Centre for Genomic Regulation (CRG). The Barcelona Institute of Science and Technology
Pol Cusco: Centre for Genomic Regulation (CRG). The Barcelona Institute of Science and Technology
Luciano Croce: Centre for Genomic Regulation (CRG). The Barcelona Institute of Science and Technology
Maria Pia Cosma: Southern Medical University
Nature Communications, 2025, vol. 16, issue 1, 1-26
Abstract:
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.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60534-6
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DOI: 10.1038/s41467-025-60534-6
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