A predictive fitness model for influenza

Nature. 2014 Mar 6;507(7490):57-61. doi: 10.1038/nature13087. Epub 2014 Feb 26.


The seasonal human influenza A/H3N2 virus undergoes rapid evolution, which produces significant year-to-year sequence turnover in the population of circulating strains. Adaptive mutations respond to human immune challenge and occur primarily in antigenic epitopes, the antibody-binding domains of the viral surface protein haemagglutinin. Here we develop a fitness model for haemagglutinin that predicts the evolution of the viral population from one year to the next. Two factors are shown to determine the fitness of a strain: adaptive epitope changes and deleterious mutations outside the epitopes. We infer both fitness components for the strains circulating in a given year, using population-genetic data of all previous strains. From fitness and frequency of each strain, we predict the frequency of its descendent strains in the following year. This fitness model maps the adaptive history of influenza A and suggests a principled method for vaccine selection. Our results call for a more comprehensive epidemiology of influenza and other fast-evolving pathogens that integrates antigenic phenotypes with other viral functions coupled by genetic linkage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Computer Simulation
  • Epitopes / genetics
  • Epitopes / immunology
  • Evolution, Molecular*
  • Genes, Viral / genetics
  • Genetic Fitness / genetics
  • Genetic Fitness / immunology
  • Genetic Fitness / physiology
  • Genetics, Population
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Influenza A Virus, H3N2 Subtype / chemistry
  • Influenza A Virus, H3N2 Subtype / classification
  • Influenza A Virus, H3N2 Subtype / genetics*
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Influenza, Human / epidemiology
  • Influenza, Human / immunology
  • Influenza, Human / virology*
  • Models, Immunological
  • Mutation / genetics
  • Time Factors


  • Epitopes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines