Predicting the evolution of human influenza A

We studied the evolution of the HA1 domain of the H3 hemagglutinin gene fro m human influenza virus type A. The phylogeny of these genes showed a singl e dominant lineage persisting over time. We tested the hypothesis that the progenitors of this single evolutionarily successful lineage were viruses c arrying mutations at codons at which prior mutations had helped the virus t o avoid human immune surveillance. We found evidence that eighteen hemagglu tinin codons appeared to have been under positive selection to change the a mino acid they encoded in the past. Retrospective tests show that viral lin eages undergoing the greatest number of mutations in the positively selecte d codons were the progenitors of future H3 lineages in nine of eleven recen t influenza seasons. Codons under positive selection were associated with a ntibody combining sites A or B or the sialic acid receptor binding site. Ho wever, not all codons in these sites had predictive value. Monitoring new H 3 isolates for additional changes in positively selected codons might help identify the most fit extant viral strains that arise during antigenic drif t.