The Roles of Competition and Mutation in Shaping Antigenic and Genetic Diversity in Influenza

Abstract

Influenza A (H3N2) offers a well-studied, yet not fully understood, disease in terms of the interactions between pathogen population dynamics, epidemiology and genetics. A major open question is why the virus population is globally dominated by a single and very recently diverged (2–8 years) lineage. Classically, this has been modeled by limiting the generation of new successful antigenic variants, such that only a small subset of progeny acquire the necessary mutations to evade host immunity. An alternative approach was recently suggested by Recker et al. in which a limited number of antigenic variants are continuously generated, but most of these are suppressed by pre-existing host population immunity. Here we develop a framework spanning the regimes described above to explore the impact of rates of mutation and levels of competition on phylodynamic patterns. We find that the evolutionary dynamics of the subtype H3N2 influenza is most easily generated within this framework when it is mutation limited as well as being under strong immune selection at a number of epitope regions of limited diversity.

Global circulation patterns of seasonal influenza viruses vary with antigenic drift

“…8b). This finding is in line with theoretical work showing that epidemiological processes can influence influenza virus evolution 19,20 . However, there are important virological differences between influenza viruses that are likely to impact the efficiency and tempo at which antigenic variation is generated and fixed, which could in turn affect epidemiology 21-24 (Supplementary Information).…”

Evolution-informed forecasting of seasonal influenza A (H3N2)

“…Prediction of multiannual temporal patterns over multiple seasons was shown possible after the observation of such an event and as long as another one did not recur, which is an impediment to real-time forecasting. A number of more mechanistic models coupling evolution and transmission dynamics have also been developed to address theoretical questions on the phylodynamics of seasonal influenza (6, 7, 10, 12). Because these individual-based, stochastic formulations are high-dimensional and computationally expensive to work with, they are not well-suited for the repeated estimation of parameters from time series data on reported cases or for epidemiological prediction.…”

Analyses of Evolutionary Characteristics of the Hemagglutinin-Esterase Gene of Influenza C Virus during a Period of 68 Years Reveals Evolutionary Patterns Different from Influenza A and B Viruses

“…After the appropriate removal of burn-in (10% of samples), a summary maximum clade credibility (MCC) tree was inferred. The MCC trees were also used to estimate the time to the most recent common ancestor (tMRCA) among contemporaneous (same year) and posterior (at least three years) strains [47,48]. tMRCA of influenza A/H1N1 (before 2009) and influenza A/H1N1pdm (in or after 2009) was calculated separately because the A/H1N1pdm virus is not directly descended from the previously-circulating A/H1N1 seasonal virus [43].…”