Immune response and within-host viral evolution: Immune response can accelerate evolution

The objectives of this paper are to explore the impact of immune response on within-host viral evolution towards higher Darwinian fitness and, in particular, to verify a hypothesis that immune response, which is insufficient to annihilate a viral infection, can accelerate this evolution. To address this issue, a model of within-host viral evolution with immune response is formulated. This model is an extension of a continuous phenotype space model of viral evolution that was earlier suggested by A. Korobeinikov and C. Dempsey, which incorporates strain-specific immune response with cross-immunity. The model is based upon Nowak-May and Wodarz models of within-host HIV dynamics and is mechanistic (based upon first principles); this allows straightforward interpretation of the model's parameters and simulation results, as well as its further developments. In order to make the simulation results and conclusions robust and reliable and to ensure that they do not depend on the particularities of an immune response model, four different mathematical models of cell-mediated immune response are considered with the proposed model. Simulations confirmed that immune response, when it is unable to eliminate viruses, accelerates viral evolution.