Physical Principles of Retroviral Integration in the Human Genome

D. Michieletto, M. Lusic, D. Marenduzzo, E. Orlandini

Research output: Contribution to journalArticlepeer-review

Abstract

Certain retroviruses, including HIV, insert their DNA in a non-random fraction of the host genome via poorly understood selection mechanisms. Here, we develop a biophysical model for retroviral integration as stochastic and quasi-equilibrium topological reconnections between polymers. We discover that physical effects, such as DNA accessibility and elasticity, play important and universal roles in this process. Our simulations predict that integration is favoured within nucleosomal and flexible DNA, in line with experiments, and that these biases arise due to competing energy barriers associated with DNA deformations. By considering a long chromosomal region in human T-cells during interphase, we discover that at these larger scales integration sites are predominantly determined by chromatin accessibility. Finally, we propose and solve a reaction-diffusion problem that recapitulates the distribution of HIV hot-spots within T-cells. With few generic assumptions, our model can rationalise experimental observations and identifies previously unappreciated physical contributions to retroviral integration site selection.
Original languageEnglish
Article number575
Number of pages11
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 4 Feb 2019

Keywords

  • q-bio.SC
  • cond-mat.soft
  • physics.bio-ph

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