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

Highlights • A model within-host viral evolution with immune response is suggested. • The model is mechanistic and is a development of an earlier suggested model of RNA virus (HIV) evolution without immune response. • Three principal scenarios of evolution are possible for this model framework, namely (i) the development of immune resistance, (ii) evolutionary escape without the development of immune resistance, and (iii) increasing Darwinian fitness. (Please note that scenario (iii) can progress without immune response at all; evolution towards decreasing virulence of adaptation to a specific host are examples). • Impact of immune response on viral evolution in scenario (iii) is considered (Scenarios (i) and (ii) are left out of the scope). Simulations show that immune response is able to accelerate evolution in scenario (iii). • HIV is a case study. Abstract 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. [ABSTRACT FROM AUTHOR]