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Computation 2017, 5(1), 6; doi:10.3390/computation5010006

Towards a Multiscale Model of Acute HIV Infection

1
Institut Camille Jordan, UMR 5208 CNRS, University Lyon, 69622 Lyon, France
2
Laboratoire de Biométrie et Biologie Evolutive, UMR 5558, University Lyon, 69622 Lyon, France
3
Mohammadia School of Engineering, University Mohamed V, 10106 Rabat, Morocco
4
Institute of Numerical Mathematics, Russian Academy of Sciences, 119333 Moscow, Russia
5
Infection Biology Laboratory, Universitat Pompeu Fabra and ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain
6
INRIA Team Dracula, INRIA Lyon La Doua, 69603 Villeurbanne, France
7
Laboratoire Poncelet, UMI 2615 CNRS, 119002 Moscow, Russia
*
Author to whom correspondence should be addressed.
Academic Editor: Rainer Breitling
Received: 31 October 2016 / Revised: 22 December 2016 / Accepted: 3 January 2017 / Published: 10 January 2017
(This article belongs to the Special Issue Multiscale and Hybrid Modeling of the Living Systems)
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Abstract

Human Immunodeficiency Virus (HIV) infection of humans represents a complex biological system and a great challenge to public health. Novel approaches for the analysis and prediction of the infection dynamics based on a multi-scale integration of virus ontogeny and immune reactions are needed to deal with the systems’ complexity. The aim of our study is: (1) to formulate a multi-scale mathematical model of HIV infection; (2) to implement the model computationally following a hybrid approach; and (3) to calibrate the model by estimating the parameter values enabling one to reproduce the “standard” observed dynamics of HIV infection in blood during the acute phase of primary infection. The modeling approach integrates the processes of infection spread and immune responses in Lymph Nodes (LN) to that observed in blood. The spatio-temporal population dynamics of T lymphocytes in LN in response to HIV infection is governed by equations linking an intracellular regulation of the lymphocyte fate by intercellular cytokine fields. We describe the balance of proliferation, differentiation and death at a single cell level as a consequence of gene activation via multiple signaling pathways activated by IL-2, IFNa and FasL. Distinct activation thresholds are used in the model to relate different modes of cellular responses to the hierarchy of the relative levels of the cytokines. We specify a reference set of model parameter values for the fundamental processes in lymph nodes that ensures a reasonable agreement with viral load and CD4+ T cell dynamics in blood. View Full-Text
Keywords: virus infection; immune response; acute phase; HIV spread; multi-scale model; single-cell regulation; reaction-diffusion; spatial dynamics virus infection; immune response; acute phase; HIV spread; multi-scale model; single-cell regulation; reaction-diffusion; spatial dynamics
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Bouchnita, A.; Bocharov, G.; Meyerhans, A.; Volpert, V. Towards a Multiscale Model of Acute HIV Infection. Computation 2017, 5, 6.

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