Relationship of pre-1918 avian influenza HA and NP sequences to subsequent avian influenza strains.

Wild waterfowl that were captured between 1915 and 1919 and preserved in 70% ethyl alcohol were tested for influenza A virus RNA. Most of the HA1 domain of the hemagglutinin (HA) gene segment was sequenced from one bird, captured in 1917, that was infected with a virus of the same HA subtype as the 1918 human pandemic virus. The 1917 HA sequence is closely related to modern avian HA sequences, suggesting little drift in avian sequences in 80 years and that the 1918 pandemic virus probably did not acquire its hemagglutinin directly from a bird. A 151-bp fragment of the nucleoprotein gene segment was sequenced from two pre-1918 birds and compared to avian and mammalian influenza strains. The 1917 avian NP sequences are also closely related to modern avian sequences and distinct from the mammalian clade in which the 1918 NP sequence is found.