Recombination in the hemagglutinin gene of the 1918 "Spanish flu".

When gene sequences from the influenza virus that caused the 1918 pandemic were first compared with those of related viruses, they yielded few clues about its origins and virulence. Our reanalysis indicates that the hemagglutinin gene, a key virulence determinant, originated by recombination. The "globular domain" of the 1918 hemagglutinin protein was encoded by a part of a gene derived from a swine-lineage influenza, whereas the "stalk" was encoded by parts derived from a human-lineage influenza. Phylogenetic analyses showed that this recombination, which probably changed the virulence of the virus, occurred at the start of, or immediately before, the pandemic and thus may have triggered it.