Insights on influenza pathogenesis from the grave

The 1918–1919 ‘Spanish’ influenza virus caused the worst pandemic in recorded history and resulted in approximately 50 million deaths worldwide. Efforts to understand what happened and to use these insights to prevent a future similar pandemic have been ongoing since 1918. In 2005 the genome of the 1918 influenza virus was completely determined by sequencing fragments of viral RNA preserved in autopsy tissues of 1918 victims, and using reverse genetics, infectious viruses bearing some or all the 1918 virus gene segments were reconstructed. These studies have yielded much information about the origin and pathogenicity of the 1918 virus, but many questions still remain.