Questioning the evidence for genetic recombination in the 1918 'Spanish flu' virus

Worobey M, Rambaut A, Pybus OG & Robertson DL

(2002) Science 296, 211.

Viral sequences have been obtained from preserved tissues of victims of the Spanish influenza pandemic that killed over 20 million people from 1918 to 1919. In a recent reanalysis of the hemagglutinin (HA) gene of the 1918 strain it was proposed that recombination had occurred such that the majority of its globular domain (HA1) was acquired from a swine-lineage virus. It was speculated that this intra-genic recombination increased the virulence of the virus resulting in the high death rate associated with this pandemic. We assert that this is incorrect and that the apparent recombination in the 1918 HA gene is actually the result of a difference in the rate of evolution between HA1 and the HA2 stalk region among human influenza A viruses of the H1N1 subtype.

Andrew Rambaut, 2007