3 years ago

Physical Principles of HIV Integration.

Davide Marenduzzo, Marina Lusic, Davide Michieletto, Enzo Orlandini

Understanding the mechanisms underlying the non-random pattern of HIV integration within a host genome remains an unsolved problem in biophysics. To address this issue, we formulate a generic multi-scale physical framework which models viral incorporation into DNA and chromosomes as stochastic "reconnections" between 3D-proximal polymer segments. Our model naturally predicts that successful integration events occur more often within more flexible or highly bent DNA, in agreement with long-standing observations. We further find that large-scale chromosomal organisation biases integration events towards transcriptionally active genomic regions. We finally propose and solve a reaction-diffusion model which captures the observed distribution of HIV integration sites within the nuclear environment of T-cells. Our general framework can be used to predict HIV integration dynamics within different cell-lines or displaying different size, fraction of transcriptionally inactive genome and nuclear genomic arrangements.

Publisher URL: http://arxiv.org/abs/1801.04232

DOI: arXiv:1801.04232v1

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