Origin and evolution of the 1918 "Spanish" influenza virus hemagglutinin gene

The "Spanish" influenza pandemic killed over 20 million people in 1918 and 1919, making it the worst infectious pandemic in history. Here, we report t he complete sequence of the hemagglutinin (HA) gene of the 1918 virus. Infl uenza RNA for the analysis was isolated from a formalin-fixed, paraffin-emb edded lung tissue sample prepared during the autopsy of a victim of the inf luenza pandemic in 1918. Influenza RNA was also isolated from lung tissue s amples from two additional victims of the lethal 1918 influenza: one formal in-fixed, paraffin-embedded sample and one frozen sample obtained by in sit u biopsy of the lung of a victim buried in permafrost since 1918. The compl ete coding sequence of the A/South Carolina/1/18 HA gene was obtained. The HA1 domain sequence was confirmed by using the two additional isolates (A/N ew York/1/18 and A/Brevig Mission/1/18). The sequences show little variatio n. Phylogenetic analyses suggest that the 1918 virus HA gene, although more closely related to avian strains than any other mammalian sequence, is mam malian and may have been adapting in humans before 1918.