González-Almela Esther, Castells-Garcia Alvaro, Le Dily François, Merino Manuel Fernández, Carnevali Davide, Cusco Pol, Di Croce Luciano, Cosma Maria Pia
Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Centre for Genomic Regulation (CRG). The Barcelona Institute of Science and Technology, Barcelona, Spain.
Nat Commun. 2025 Jun 19;16(1):5313. doi: 10.1038/s41467-025-60534-6.
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.
1型单纯疱疹病毒（HSV-1）在裂解感染期间重塑宿主染色质结构并诱导宿主到病毒的转录转换。我们结合超分辨率成像和染色体捕获技术来确定重塑机制。我们发现宿主染色质因RNA聚合酶II（RNAP II）和拓扑异构酶I（TOP1）被劫持而发生大量浓缩。此外，HSV-1感染导致拓扑相关结构域和环的重排，尽管宿主中的A/B区室得以维持。病毒基因组的位置及其与RNAP II和黏连蛋白的关联在纳米尺度上得以确定。我们揭示了特定的宿主-HSV-1基因组相互作用以及上调的人类基因在最紧密接触区域的富集。最后，TOP1抑制完全阻断HSV-1感染，提示了可能的抗病毒策略。这种宿主染色质重新布线的病毒机制揭示了转录在染色质结构中的作用。
