Reconstruction of the 1918 pandemic influenza virus: how revealing the molecular secrets of the virus responsible for the worst pandemic in recorded history can guide our response to future influenza pandemics.

There is an ever-present threat that a pandemic will result from the emergence of a new influenza strain to which humans have little immunity. In 1957 and 1968, new influenza viruses emerged into the human population and spread globally. Those pandemics were associated with high rates of illness and mortality, but both paled in comparison with the influenza pandemic of 1918. Reconstruction of the 1918 pandemic virus and studies to elucidate the exceptional virulence of the virus will be important steps toward understanding virulent influenza strains. One approach has been to reconstruct recombinant viruses, in which genes of the 1918 virus are replaced with genes from contemporary human influenza viruses in attempts to understand which of the eight virus gene segments contribute to its high virulence. The identification of the precise pandemic virus genes associated with replication may help elucidate virulence factors for other influenza viruses with pandemic potential and, thereby, help identify targets for drug intervention. An important role of antiviral drugs during an influenza pandemic will be to slow virus replication and subsequent spread while an appropriate vaccine is in production. The topics included in this review highlight areas of active research into the understanding of what made the 1918 pandemic influenza virus so virulent and transmissible. Such research is being done with the hope that the knowledge gained will allow the world to better prepare for and respond to future influenza pandemics.