Hemagglutinin sequence clusters and the antigenic evolution of influenza A virus

Joshua B. Plotkin, Jonathan Dushoff, Simon Asher Levin

Research output: Contribution to journalArticlepeer-review

189 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)6263-6268
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - Apr 30 2002

All Science Journal Classification (ASJC) codes

  • General


  • Clustering
  • H3N2
  • Quasi species
  • Vaccination


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