Andrea Fontana — Università di Napoli "Federico II" and INFN sezione di Napoli #
Polymer physics models predict chromatin organization of SARS-CoV-2 infected cells #
It has been recently discovered that SARS-CoV-2 alters chromatin 3D structure of the host genome [1] at multiple length scales, ranging from some kilobases to entire chromosomes. We used polymer-physics models to investigate the physical mechanisms underlying such re-structuring. In particular, we showed that a polymer model with altered chromatin phase-separation properties [3] accurately captures re-arrangements upon viral infection, as emerged from experimental data. Furthermore, Molecular Dynamics (MD) simulations of the model indicate that SARS-CoV-2 infection leads to a peculiar loss of structural specificity and impacts chromatin time dynamics, reducing the stability of the regulatory contact network of key genes involved in antiviral response. Overall, our study [3] provides the first polymer-physics based reconstruction of SARS-CoV-2 infected genome with mechanistic insights on the consequent gene mis-regulation.  [1] R. Wang, et al., SARS-CoV-2 restructures host chromatin architecture. Nat. Microbiol. 2023 84 8, 679-694 (2023).   
[2] A. M. Chiariello, et al., Polymer physics of chromosome large-scale 3D organisation. Sci. Rep. 6, 29775 (2016).  [3] A. M. Chiariello, A. Abraham, S. Bianco, A. Esposito, F. Vercellone, M. Conte, A. Fontana, M. Nicodemi, Multiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells. BioRxiv (2023). https://doi.org/10.1101/ 2023.07.27.550709