HIV-1 infection kinetics in tissue cultures

Area of Science:

• Virology
• Mathematical Biology
• Computational Science

Background:

• Extensive experimental research exists on Human Immunodeficiency Virus type 1 (HIV-1).
• Theoretical modeling of HIV-1 spread in tissue culture remains underdeveloped.
• Existing models for in vivo HIV-1 infection often require unrealistic parameters to show oscillations.

Purpose of the Study:

• To develop and analyze mathematical models for HIV-1 spread in tissue culture.
• To investigate the dynamics of both cell-free and cell-to-cell HIV-1 transmission.
• To compare model predictions with experimental observations and assess their utility for interpreting data.

Main Methods:

• Utilized two systems of ordinary differential equations to model viral spread.
• Simulated viral dynamics under realistic parameter regimes.
• Analyzed model outputs for phases of viral growth, decline, extinction, and oscillation.

Main Results:

• Both cell-free and cell-to-cell transmission models predict an initial exponential viral growth phase, followed by culture extinction.
• Oscillatory viral dynamics were observed and can be explained by infection dynamics alone, without requiring biological heterogeneity.
• A proportionality was found between infected cells and cell-free virus, consistent with viral load measurement assumptions.

Conclusions:

• The developed models qualitatively mimic observed oscillations in experimental tissue infections.
• Mathematical modeling provides a framework for understanding HIV-1 spread dynamics in vitro.
• These models can enhance the interpretation of experimental data and improve extrapolation to in vivo conditions.