Modeling HIV-1 viral capsid nucleation by dynamical systems

Area of Science:

• Virology
• Biophysics
• Computational Biology

Background:

• Viral capsid assembly is crucial for viral replication, occurring in distinct nucleation and elongation stages.
• Understanding the initial nucleation phase is key to deciphering viral self-assembly mechanisms.

Purpose of the Study:

• To develop and validate mathematical models for human immunodeficiency virus type 1 (HIV-1) viral capsid nucleation.
• To investigate the influence of association and dissociation rates on capsid protein (CA) multimer concentrations during nucleation.

Main Methods:

• Development of a six-species dynamical system to model HIV-1 capsid nucleation.
• Application of the Particle Swarm Optimization (PSO) algorithm for parameter fitting using experimental data.
• Numerical simulations to analyze CA multimer concentrations and perform sensitivity analysis.

Main Results:

• Simulated CA multimer concentrations showed strong agreement with experimental data.
• Sensitivity analysis highlighted the significant impact of association and dissociation rates on nucleation dynamics.
• Identified CA trimer-of-dimers as a critical component in the HIV-1 capsid nucleation stage.

Conclusions:

• The developed mathematical models accurately represent HIV-1 capsid nucleation.
• The study underscores the importance of specific CA multimer structures, like trimer-of-dimers, in initiating viral assembly.
• Findings provide insights into the fundamental processes governing viral capsid formation.