Fontana Andrea, Bianco Simona, Tafuri Fabrizio, Esposito Andrea, Abraham Alex, Conte Mattia, Vercellone Francesca, Di Pierno Florinda, Kundu Sumanta, Guha Sougata, Di Carluccio Ciro, Prisco Antonella, Nicodemi Mario, Chiariello Andrea M
Dipartimento di Fisica, Università degli Studi di Napoli Federico II, and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy.
Dipartimento di Ingegneria Chimica dei Materiali e della Produzione Industriale - DICMaPI, Università degli Studi di Napoli Federico II, and INFN Napoli, Piazzale Vincenzo Tecchio 80, 80125 Naples, Italy.
J Chem Phys. 2025 Jan 7;162(1). doi: 10.1063/5.0243454.
In the last years, it has been proved that some viruses are able to re-structure chromatin organization and alter the epigenomic landscape of the host genome. In addition, they are able to affect the physical mechanisms shaping chromatin 3D structure, with a consequent impact on gene activity. Here, we investigate with polymer physics genome re-organization of the host genome upon SARS-CoV-2 viral infection and how it can impact structural variability within the population of single-cell chromatin configurations. Using published Hi-C data and molecular dynamics simulations, we build ensembles of 3D configurations representing single-cell chromatin conformations in control and SARS-CoV-2 infected conditions. We focus on genomic length scales of TADs and consider, as a case study, models of real loci containing DDX58 and IL6 genes, belonging, respectively, to the antiviral interferon response and pro-inflammatory genes. Clustering analysis applied to the ensemble of polymer configurations reveals a generally increased variability and a more heterogeneous population of 3D structures in infected conditions. This points toward a scenario in which viral infection leads to a loss of chromatin structural specificity with, likely, a consequent impact on the correct regulation of host cell genes.
在过去几年中，已证实一些病毒能够重新构建染色质组织并改变宿主基因组的表观基因组格局。此外，它们能够影响塑造染色质三维结构的物理机制，从而对基因活性产生影响。在此，我们运用高分子物理学方法研究了SARS-CoV-2病毒感染后宿主基因组的重新组织情况，以及它如何影响单细胞染色质构型群体中的结构变异性。利用已发表的Hi-C数据和分子动力学模拟，我们构建了代表对照和SARS-CoV-2感染条件下单细胞染色质构象的三维构型集合。我们关注拓扑相关结构域（TAD）的基因组长度尺度，并以分别属于抗病毒干扰素反应基因和促炎基因的包含DDX58和IL6基因的真实基因座模型作为案例研究。对聚合物构型集合进行的聚类分析表明，在感染条件下，三维结构的变异性普遍增加，群体更加异质。这表明病毒感染导致染色质结构特异性丧失，可能进而影响宿主细胞基因的正确调控。
