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A new method for constructing the multi-modal impacts on the immune systemin the chronic phase of viral infection, based on mathematical models formulated with delay-differential equations is proposed. The so called, optimal disturbances, widely used in the aerodynamic stability theory for mathematical models without delays are constructed for perturbing the steady states of the dynamical system for maximizing the perturbation-induced response. The concept of optimal disturbances is generalized on the systems with delayed argument. An algorithm for computing the optimal disturbances is developed for such systems. The elaborated computational technology is tested on a system of four nonlinear delay-differential equations which represents the model of experimental infection in mice caused by lymphocytic choriomeningitis virus. The steady-state perturbations resulting in a maximum responsewere computed with the proposed algorithm for two types of steady states characterized by a low and a high levels of viral load. The possibility of correction of the infection dynamics and the restoration of virus-specific lymphocyte functioning of the immune system by perturbing the steady states is demonstrated.

Maximum response perturbation-based control of virus infection model with time-delays