"The Search for the 1918 Spanish Influenza Virus"
The 'Spanish' influenza pandemic killed approximately 40 million people in 1918-19, making it the worst infectious disease outbreak in history. However, the virus responsible was not isolated. Understanding the origins of the 1918 virus, and the basis for its exceptional virulence, may have utility in the prediction of future influenza pandemics. Using modern molecular biology techniques, characterization of the 1918 virus can now be performed. RNA from the 1918 flu virus was isolated from formalin-fixed, paraffin-embedded lung tissue samples of victims of the 1918 influenza that had been stored in the archives of the Armed Forces Institute of Pathology (Washington, DC), and from frozen lung tissue of a victim buried in permafrost in Alaska. The sequences are consistent with a novel H1N1 influenza A virus. Analyses suggest that the 1918 virus belongs to the subgroup of influenza strains that infect humans and swine, not the avian subgroup. Recently we reported the complete sequence of the hemagglutinin gene of the 1918 virus. The sequences from the three cases show very little variation. Phylogenetic analyses suggest that the 1918 virus hemagglutinin gene, although more closely related to avian strains than any other mammalian H1 sequence, is mammalian, and may have already been adapting in humans before 1918.