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Mathematical Modeling of HIV Replication and the Response of the Interferon System

  • MOLECULAR BIOLOGY OF THE CELL
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Abstract—Developing physiologically meaningful mathematical models that describe multilevel regulation in a complex network of immune processes, in particular, of the system of interferon-regulated virus production processes, is a fundamental scientific problem, within the framework of an interdisciplinary systems approach to research in immunology. Here, we have presented a detailed high-dimensional model describing HIV (human immunodeficiency virus) replication, the response of type I interferon (IFN) to the virus infection of the cell, and suppression of the action of IFN-induced proteins by HIV accessory proteins. As a result, this model includes interactions of all three processes for the first time. The mathematical model is a system of 37 nonlinear ordinary differential equations including 78 parameters. Importantly, the model describes not only the processes of the IFN response of the cell to virus infection, but also the mechanisms used by the virus to prevent effects of the IFN system.

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ACKNOWLEDGMENTS

The authors are grateful to the reviewers and editors for important comments and corrections during the work on the article.

Funding

The work was carried out within the framework of the State Assignment (project FWNF-2022-0015; I.A. Gainova) and with the financial support of the Russian Foundation for Basic Research (grant no. 20-01-00352; A.E. Soboleva, D.S. Grebennikov, G.A. Bocharov).

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Authors and Affiliations

  1. Sobolev Institute of Mathematics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    I. A. Gainova

  2. Moscow Institute of Physics and Technology (National Research University, 141701, Dolgoprudny, Moscow Region, Russia

    A. E. Soboleva

  3. Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences, 119333, Moscow, Russia

    D. S. Grebennikov & G. A. Bocharov

  4. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, 119991, Moscow, Russia

    D. S. Grebennikov & G. A. Bocharov

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  1. I. A. Gainova
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  2. A. E. Soboleva
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  3. D. S. Grebennikov
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  4. G. A. Bocharov
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Correspondence to I. A. Gainova.

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The authors declare that they have no conflicts of interest. This article does not contain any studies involving humans or animals as research subjects.

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Abbreviations: HIV, human immunodeficiency virus; IFN, interferon(s); cDNA, complementary DNA; dsRNA, double-spliced RNA; gRNA, genomic RNA; full-length RNA; ISGs, interferon-stimulated genes; ssRNA, single-spliced RNA.

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Gainova, I.A., Soboleva, A.E., Grebennikov, D.S. et al. Mathematical Modeling of HIV Replication and the Response of the Interferon System. Mol Biol 57, 700–713 (2023). https://doi.org/10.1134/S0026893323040076

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  • DOI: https://doi.org/10.1134/S0026893323040076

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