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

Area of Science:

• Virology
• Immunology
• Mathematical Biology
• Computational Immunology

Background:

• The human immunodeficiency virus Type 1 (HIV-1) life cycle involves complex interactions within CD4 T cells.
• The intracellular Type I interferon (IFN-I) response plays a crucial role in antiviral defense.
• HIV-1 employs viral proteins to counteract host antiviral mechanisms, including IFN-I.

Purpose of the Study:

• To construct and calibrate a mathematical model of the HIV-1 life cycle in CD4 T cells.
• To elucidate the mechanisms of IFN-I-induced suppression of HIV-1 replication.
• To investigate the interplay between viral proteins (Vpu, Vif) and interferon-induced antiviral factors.

Main Methods:

• Development of both deterministic and stochastic mathematical models for HIV-1 replication dynamics.
• Calibration of the model using existing biological data.
• Utilizing the stochastic model to predict the efficiency of IFN-I suppression under various conditions and evaluate virion excretion probabilities.

Main Results:

• The model accurately describes the activation of the intracellular IFN-I response and its suppressive effects on viral replication.
• It quantifies the inactivation of antiviral factors by HIV-1 Vpu and Vif proteins.
• Predictions were made regarding the efficiency of IFN-I-induced suppression for different initial conditions (autocrine/paracrine effects), MOIs, and IFN-I concentrations, characterizing heterogeneity in viral and IFN-I production.

Conclusions:

• Mathematical modeling provides a powerful tool to understand the complex dynamics of HIV-1 infection and host immune response.
• The study highlights the critical role of Type I interferon in controlling HIV-1 replication.
• The findings offer insights into viral evasion strategies and the quantitative aspects of antiviral immunity.