Hemagglutinin sequence clusters and the antigenic evolution of influenza A virus

Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6263-8. doi: 10.1073/pnas.082110799. Epub 2002 Apr 23.

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.

Publication types

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

MeSH terms

  • Antibodies / metabolism
  • Binding Sites
  • Databases as Topic
  • Genotype
  • Hemagglutinins / genetics*
  • Influenza A virus / genetics*
  • Influenza Vaccines / genetics
  • Models, Genetic
  • Multigene Family
  • Mutation*
  • Time Factors
  • Vaccines / genetics*

Substances

  • Antibodies
  • Hemagglutinins
  • Influenza Vaccines
  • Vaccines