Stochastic Modelling of HIV-1 Replication in a CD4 T Cell with an IFN Response

Igor Sazonov; Dmitry Grebennikov; Rostislav Savinkov; Arina Soboleva; Kirill Pavlishin; Andreas Meyerhans; Gennady Bocharov

doi:10.3390/v15020296

Stochastic Modelling of HIV-1 Replication in a CD4 T Cell with an IFN Response

Viruses. 2023 Jan 20;15(2):296. doi: 10.3390/v15020296.

Authors

Igor Sazonov¹, Dmitry Grebennikov^{2

3

4}, Rostislav Savinkov^{2

3

5}, Arina Soboleva⁶, Kirill Pavlishin⁷, Andreas Meyerhans^{8

9}, Gennady Bocharov^{2

3

5}

Affiliations

¹ Faculty of Science and Engineering, Swansea University, Bay Campus, Fabian Way SA1 8EN, UK.
² Marchuk Institute of Numerical Mathematics of the RAS, 119333 Moscow, Russia.
³ Moscow Center of Fundamental and Applied Mathematics at INM RAS, 119333 Moscow, Russia.
⁴ World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
⁵ Institute for Computer Science and Mathematical Modelling, Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
⁶ Department of Control and Applied Mathematics, Moscow Institute of Physics and Technology (National Research University), 141701 Dolgoprudny, Russia.
⁷ Faculty of Computational Mathematics and Cybernetics, Lomonosov Moscow State University, 119991 Moscow, Russia.
⁸ I CREA, Pg. Lluis Companys 23, 08010 Barcelona, Spain.
⁹ Infection Biology Laboratory, Universitat Pompeu Fabra, 08003 Barcelona, Spain.

Abstract

A mathematical model of the human immunodeficiency virus Type 1 (HIV-1) life cycle in CD4 T cells was constructed and calibrated. It describes the activation of the intracellular Type I interferon (IFN-I) response and the IFN-induced suppression of viral replication. The model includes viral replication inhibition by interferon-induced antiviral factors and their inactivation by the viral proteins Vpu and Vif. Both deterministic and stochastic model formulations are presented. The stochastic model was used to predict efficiency of IFN-I-induced suppression of viral replication in different initial conditions for autocrine and paracrine effects. The probability of virion excretion for various MOIs and various amounts of IFN-I was evaluated and the statistical properties of the heterogeneity of HIV-1 and IFN-I production characterised.

Keywords: HIV life cycle; Markov chain Monte Carlo method; Type I interferon (IFN-I); mathematical model; sensitivity analysis; stochastic processes; viral dynamics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies
CD4-Positive T-Lymphocytes
HIV-1*
Humans
Interferon Type I*
Virus Replication

Substances

Antibodies
Interferon Type I

Grants and funding

This research was funded by the Russian Science Foundation (Grant Number 18-11-00171) and partly by the Russian Foundation for Basic Research according to the research project number 20-01-00352. A.M. is also supported by the Spanish Ministry of Science and Innovation Grant No. PID2019-106323RB-I00 AEI//10.13039/501100011033 and “Unidad de Excelencia María de Maeztu” funded by the AEI (CEX2018-000792-M). G.B., D.G. and R.S. were partly supported by the Moscow Center for Fundamental and Applied Mathematics (agreement with the Ministry of Education and Science of the Russian Federation No. 075-15-2022-286).