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 associated with DNA insertions. By coupling our model to a well-established framework for large-scale 3D URLanisation we discover that the non-random integration of HIV in human chromatin may be explained as due to large-scale accessibilityof 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 .
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 integrations 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 .
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The Human Immunodeficiency Virus (HIV) integrates its genetic material in a small and
Certain retroviruses, including HIV, insert their DNA in a
D
all possible integration sites along
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. 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
via poorly understood selection mechanisms. Here, we develop a biophysical model for retroviral integrations as stochastic and
A
topological reconnections between polymers. We discover that physical effects, such as DNA accessibility and elasticity, play important and universal roles in this
R
model rationalises a number of long-standing unexplained observations: we show that HIV
simulations predict that
R
in nucleosomal rather than naked DNA, and in flexible over rigid DNA. We find
within nucleosomal and flexible DNA, in line with experiments, and
R
the difference in the bending energy barrier
competing energy barriers
R
insertions. By coupling our model to a well-established framework for large-scale 3D URLanisation
deformations. By considering a long chromosomal region in human T-cells during interphase,
R
the non-random integration of HIV in human chromatin may be explained as due to large-scale accessibilityof interphase chromosomes. Finally
at these larger scales integration sites are predominantly determined by chromatin accessibility. Finally,
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model
problem
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the nucleus of human
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explain much of the current evidence on HIV integration and may be used to predict integration patterns in human cells
rationalise experimental observations and identifies previously unappreciated physical contributions to retroviral integration site selection