title: Hemagglutinin sequence clusters and the antigenic evolution of influenza A virus.
abstract: Continual mutations to the hemagglutinin (HA) gene of influenza A virus generate novel antigenic strains that cause annual epidemics. Using a database of 560 viral RNA sequences, we study the structure and tempo of HA evolution over the past two decades. We detect a critical length scale, in amino acid space, at which HA sequences aggregate into clusters, or swarms. We investigate the spatio-temporal distribution of viral swarms and compare it to the time series of the influenza vaccines recommended by the World Health Organization. We introduce a method for predicting future dominant HA amino acid sequences and discuss its potential relevance to vaccine choice. We also investigate the relationship between cluster structure and the primary antibody-combining regions of the HA protein.
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08540, USA. plotkin@ias.edu
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Plotkin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dushoff
authors.forename: Simon A
authors.initials: SA
authors.lastname: Levin
mesh_terms: D000906:Antibodies / Q000378:metabolism; D001665:Binding Sites; D019992:Databases as Topic; D005838:Genotype; D006388:Hemagglutinins / Q000235:genetics*; D009980:Influenza A virus / Q000235:genetics*; D007252:Influenza Vaccines / Q000235:genetics; D008957:Models, Genetic; D005810:Multigene Family; D009154:Mutation; D013997:Time Factors; D014612:Vaccines / Q000235:genetics*
chemical_list: D000906:Antibodies; D006388:Hemagglutinins; D007252:Influenza Vaccines; D014612:Vaccines