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The dynamics of a general in-host model with intracellular delay is studied. The model can describe in vivo infections of HIV-I, HCV, and HBV. It can also be considered as a model for HTLV-I infection. We derive the basic reproduction number R0 for the viral infection, and establish that the global dynamics are completely determined by the values of R0. If R0 < or = 1, the infection-free equilibrium is globally asymptotically stable, and the virus are cleared. If R0 > 1, then the infection persists and the chronic-infection equilibrium is locally asymptotically stable. Furthermore, using the method of Lyapunov functional, we prove that the chronic-infection equilibrium is globally asymptotically stable when R0 > 1. Our results shows that for intercellular delays to generate sustained oscillations in in-host models it is necessary have a logistic mitosis term in target-cell compartments.

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The dynamics of an in-host model with general form of target-cell dynamics, nonlinear incidence, and distributed delay are investigated. The model can describe the in vivo infection dynamics of many viruses such as HIV-I, HCV, and HBV. We derive the basic reproduction number R 0 for the viral infection and establish that the global dynamics are completely determined by the values of R 0 : if R 0 ≤ 1, the infection-free equilibrium is globally asymptotically stable, and the virus is cleared; if R 0 > 1, then the infection persists, and the chronic-infection equilibrium is globally asymptotically stable. An implication of our results is that intracellular delays will lead to periodic oscillations in in-host models only with the right kind of target-cell dynamics.

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Sustained and transient oscillations are frequently observed in clinical data for immune responses in viral infections such as human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. To account for these oscillations, we incorporate the time lag needed for the expansion of immune cells into an immunosuppressive infection model. It is shown that the delayed antiviral immune response can induce sustained periodic oscillations, transient oscillations and even sustained aperiodic oscillations (chaos). Both local and global Hopf bifurcation theorems are applied to show the existence of periodic solutions, which are illustrated by bifurcation diagrams and numerical simulations. Two types of bistability are shown to be possible: (i) a stable equilibrium can coexist with another stable equilibrium, and (ii) a stable equilibrium can coexist with a stable periodic solution.

To understand joint effects of logistic growth in target cells and intracellular delay on viral dynamics in vivo, we carry out two-parameter bifurcation analysis of an in-host model that describes infections of many viruses including HIV-I, HBV and HTLV-I. The bifurcation parameters are the mitosis rate r of the target cells and an intracellular delay τ in the incidence of viral infection. We describe the stability region of the chronic-infection equilibrium E* in the two-dimensional (r, τ) parameter space, as well as the global Hopf bifurcation curves as each of τ and r varies. Our analysis shows that, while both τ and r can destabilize E* and cause Hopf bifurcations, they do behave differently. The intracellular delay τ can cause Hopf bifurcations only when r is positive and sufficiently large, while r can cause Hopf bifurcations even when τ = 0. Intracellular delay τ can cause stability switches in E* while r does not.

Stable periodic oscillations have been shown to exist in mathematical models for the CTL response to HTLV-I infection. These periodic oscillations can be the result of mitosis of infected target CD4(+) cells, of a general form of response function, or of time delays in the CTL response. In this study, we show through a simple mathematical model that time delays in the CTL response process to HTLV-I infection can lead to the coexistence of multiple stable periodic solutions, which differ in amplitude and period, with their own basins of attraction. Our results imply that the dynamic interactions between the CTL immune response and HTLV-I infection are very complex, and that multi-stability in CTL response dynamics can exist in the form of coexisting stable oscillations instead of stable equilibria. Biologically, our findings imply that different routes or initial dosages of the viral infection may lead to quantitatively and qualitatively different outcomes.