Delayed immune responses and heterogeneous exposure shape within-host viral dynamics.

Area of Science:

• Mathematical Biology
• Immunology
• Virology

Background:

• Understanding within-host viral dynamics is crucial for developing effective antiviral therapies.
• Immune responses and pathogen exposure patterns significantly influence viral load and disease progression.
• Delayed feedback mechanisms in biological systems can lead to complex and counterintuitive dynamics.

Purpose of the Study:

• To develop and analyze a delayed within-host viral dynamics model incorporating nonlinear immune responses and heterogeneous exposure.
• To investigate the impact of different immune response architectures and exposure profiles on viral dynamics.
• To identify key factors governing viral persistence and clearance efficiency.

Main Methods:

• A delayed within-host viral dynamics model with logistic viral replication and immune-mediated clearance was formulated.
• A 4x4 factorial framework coupled four immune response types with four exposure profiles, creating sixteen scenarios.
• Theoretical analysis (positivity, boundedness, bifurcations) and extensive numerical simulations were performed.

Main Results:

• Immune sensitivity and exposure intermittence, rather than maximal clearance capacity, determined viral dynamics hierarchies.
• Ultrasensitive immune responses amplified early viral overshoots and cumulative burden.
• Impulsive or adaptive exposure profiles reduced viral persistence and accelerated decay.

Conclusions:

• Delayed immune feedback systems exhibit complex dynamics influenced by immune sensitivity and exposure patterns.
• Trade-offs exist between early viral control and long-term viral persistence.
• Model findings offer insights into optimizing therapeutic strategies by considering immune response characteristics and exposure timing.