Antigenic evolution of viruses in host populations

Spread of many RNA viruses in a population represents a competition between host immune responses and viral evolution. RNA viruses accumulate mutations in immunologically important regions to escape immune recognition in hosts previously exposed to infection, while the immune system responds by producing new memory cells. Despite recent advances in data collection and their analysis, it remains conceptually unclear how epidemiology, immune response, and evolutionary factors interact to produce the observed speed of evolution and its incidence. By combining the standard epidemiological approach with the modern theory of viral evolution, we predict a general relationship between long-term cross-immunity, antigenic diversity of virus, its evolution speed, infection incidence, and the time to the most recent common ancestor. We apply these theoretical findings to available data on influenza A H3N2 to determine two important parameters of H3N2 evolution and confirm the model. Current strategies of vaccination against influenza should take into account stochastic fluctuations in fitness effect of mutations predicted by the theory