Global Properties of Nested Network Model with Application to Multi-Epitope HIV/CTL Dynamics

TL;DR

This paper extends a nested network model to analyze within-host HIV and CTL immune response dynamics, providing insights into viral escape, immune hierarchy, and system stability through mathematical analysis and simulations.

Contribution

It generalizes existing ecological network models to HIV/CTL interactions, revealing stable coexistence and evolutionary patterns within the host.

Findings

Model captures viral escape and immune hierarchy.

Lyapunov function characterizes system stability.

Numerical simulations support theoretical results.

Abstract

Mathematical modeling and analysis can provide insight on the dynamics of ecosystems which maintain biodiversity in the face of competitive and prey-predator interactions. Of primary interests are the underlying structure and features which stabilize diverse ecological networks. Recently Korytowski and Smith [17] proved that a perfectly nested infection network, along with appropriate life history trade-offs, leads to coexistence and persistence of bacteria-phage communities in a chemostat model. In this article, we generalize their model in order to apply it to the within-host dynamics virus and immune response, in particular HIV and CTL (Cytotoxic T Lymphocyte) cells. Our model can produce a diverse hierarchy of viral and immune populations, built through sequential viral escape from dominant immune responses and rise in subdominant immune responses, consistent with observed patterns of HIV/CTL evolution. We find a Lyapunov function for the system which leads to rigorous characterization of persistent viral and immune variants, and informs upon equilibria stability and global dynamics. Results are interpreted in the context of within-host HIV/CTL evolution and numerical simulations are provided.