Figure 3. Schematic representation of the HIV immune activation model and the control model.

(A) Model of the cellular immune response against HIV. In the absence of immune activation, pools of resting T_H (CD4) cells, CTLs (CD8), and pAPCs divide at rates, ρ₄, ρ₈, ρ_D and die at rates , , and , reaching homeostatic concentrations , , and , respectively. Activated T_H cells become infected through contact with free virions at a rate constant σ, whereas resting cells are assumed to be non-susceptible to the virus. T_H cells are activated at a rate constant a₄ after contacting a pAPC with an HIV epitope or by other antigens at rate constant b (background activation). T_H cells establishing synapses with pAPCs have a probability d of being concomitantly infected with the same viral type. Infected cells release virions at a rate constant α and die at a rate constant . CTL pre-activation occurs after contacting infected cells (a₈) or pAPCs (a_8D). A co-stimulatory signal from activated T_H cells is necessary for completing CTL activation (a_8′). Infected cells are lysed by CTLs at a rate constant k. Death rate constants for activated T_H cells , CTLs , and pAPCs and virion inactivation rates (Γ_V) are not shown for simplicity. The full list of variables and parameters is available in Appendix S1, which also provides references to empirical work justifying the parameter values used (see also main text). A fraction μ of the virions released in each cell infection become escape mutants. Avoidance of CTL activation or CTL-mediated killing leads to CTL escape (red bars), whereas avoidance of T_H cell activation leads to T_H escape (blue bars). The model allows full T-cell (purple), T_H-only (blue), and CTL-only (red) escape mutants. (B) Control model in which the virus targets a nonimmune cell type C (e.g., hepatocytes, epithelial cells, etc.) instead of T_H cells. Two key differences with the HIV model are that viral replication is not dependent upon immune activation and that transinfection does not take place. Variables, parameters, and equations for this model are also shown in Appendix S1.