Global stability of secondary DENV infection models with non-specific and strain-specific CTLs

Abstract

Dengue virus (DENV) is a highly perilous virus that is transmitted to humans through mosquito bites and causes dengue fever. Consequently, extensive efforts are being made to develop effective treatments and vaccines. Mathematical modeling plays a significant role in comprehending the dynamics of DENV within a host in the presence of cytotoxic T lymphocytes (CTL) immune response. This study examines two models for secondary DENV infections that elucidate the dynamics of DENV under the influence of two types of CTL responses, namely non-specific and strain-specific responses. The first model encompasses five compartments, which consist of uninfected monocytes, infected monocytes, free DENV particles, non-specific CTLs, and strain-specific CTLs. In the second model, latently infected cells are introduced into the model. We posit that the CTL responsiveness is determined by a combination of self-regulating CTL response and a predator-prey-like CTL response. The model's solutions are verified to be nonnegativity and bounded and the model possesses two equilibrium states: the uninfected equilibrium EQ0 and the infected equilibrium EQ⁎. Furthermore, we calculate the basic reproduction number R0, which determines the existence and stability of the model's equilibria. We examine the global stability by constructing suitable Lyapunov functions. Our analysis reveals that if R0≤1, then EQ0 is globally asymptotically stable (G.A.S), and if R0>1, then EQ0 is unstable while EQ⁎ is G.A.S. To illustrate our findings analytically, we conduct numerical simulations for each model. Additionally, we perform sensitivity analysis to demonstrate how the parameter values of the proposed model impact R0 given a set of data. Finally, we discuss the implications of including the CTL immune response and latently infected cells in the secondary DENV infection model. Our study demonstrates that incorporating the CTL immune response and latently infected cells diminishes R0 and enhances the system's stability around EQ0.