Emergence of a C-Terminal Seven-Amino-Acid Elongation of NS1 in Around 1950 Conferred a Minor Growth Advantage to Former Seasonal Influenza A Viruses

Influenza A viruses circulating in humans from similar to 1950 to similar to 1987 featured a nonstructural (NS1) protein with a C-terminal extension of seven amino acids. The biological significance of this NS1 elongation remained elusive. We observed that replication kinetics of the wild-type virus A/Hong Kong/01/68 (H3N2) and a mutant encoding a truncated NS1 were indistinguishable in most experimental systems. However, wild-type virus outcompeted the mutant during mixed infections, suggesting that the NS1 extension conferred minor growth advantages.