Science · 1999 · 536 citations · 5 references
Life SciencesEvolutionary BiologyMolecular BiologyMolecular EvolutionMolecular VirologyVirologyCodon EvolutionCodon RecognitionPathogen EvolutionViral EvolutionViral GeneticsViral GenomicsAdaptive Codon EvolutionHemagglutinin-receptor BindingLineage-specific Codon EvolutionPositive Predictive ValuePositive SelectionSialic Acid RecognitionSite-specific Codon EvolutionViral Antigenic Drift
The study proposes monitoring changes in positively selected HA1 codons of H3 isolates to pinpoint the most fit viral strains during antigenic drift. Eighteen HA1 codons under positive selection were identified, and lineages with many mutations in these sites predicted future H3 strains in 9 of 11 seasons, though not all sites were predictive.
Eighteen codons in the HA1 domain of the hemagglutinin genes of human influenza A subtype H3 appear to be under positive selection to change the amino acid they encode. Retrospective tests show that viral lineages undergoing the greatest number of mutations in the positively selected codons were the progenitors of future H3 lineages in 9 of 11 recent influenza seasons. Codons under positive selection were associated with antibody combining site A or B or the sialic acid receptor binding site. However, not all codons in these sites had predictive value. Monitoring new H3 isolates for additional changes in positively selected codons might help identify the most fit extant viral strains that arise during antigenic drift.
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Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid
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