Long-term experimental evolution of seasonal influenza A/H3N2 virus reveals diverse evolutionary potential

Serial passaging of seasonal influenza A/H3N2 for 1,200 generations in differentiated human airway epithelium shows variant accumulation rates differ significantly among culture lines.

• Why it matters: Predicting influenza evolution depends on whether outcomes are reproducible, but the role of selective context versus intrinsic constraints remains unclear.
• What they did: Replicate A/H3N2 populations were serially passaged across 12 independent differentiated human airway epithelium culture lines (three replicates of four donors) with adaptive immune selection removed, then deep sequencing reconstructed dynamics.
• The result: Parallel evolution was minimal, and evolution produced polymorphisms absent from global human populations, reversions to historical sequences, and changes at positions near-invariant globally since 1968.