Physical Principles of HIV Integration in the Human Genome
Year: 2018
Type: preprint
Abstract: The Human Immunodeficiency Virus (HIV) integrates its genetic material in a small and non-random fraction of all possible integration sites along the host genome. The mechanisms driving this non-uniform selection are not known. To address this issue, we formulate a generic physical model where we treat the viral incorporation into DNA and chromosomes as a stochastic quasi-equilibrium process. Our model rationalises a number of long-standing unexplained observations: we show that HIV integration is favoured in nucleosomal rather than naked DNA, and in flexible over rigid DNA. We find that these biases arise due to the difference in the bending energy barrier asso- ciated with DNA insertions. By coupling our model to a well-established framework for large-scale 3D genome organisation we discover that the non-random integration of HIV in human chromatin may be explained as due to large-scale accessibility of interphase chromosomes. Finally we propose and solve a reaction-diffusion model that recapitulates the distribution of HIV hot-spots within the nucleus of human T-cells. With few generic assumptions, our model can explain much of the current evidence on HIV integration and may be used to predict integration patterns in human cells.
Source: arXiv (Cornell University)
Institution: University of Edinburgh
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2953007896