The reconstruction of all eight gene segments of the pandemic virus provided the opportunity to find out what genomics could reveal about the high-virulence phenotype of the 1918 virus. The initial characterization of this virus by Terrence Tumpey and colleagues demonstrated that it highly virulent in mice and most animals died within five days after infection [33] . Genomic analyses, led by John Kash, showed that animals infected with the reconstructed virus showed an increased and accelerated activation of genes associated with pro-inflammatory and celldeath pathways by 24 h after infection [34] . Significantly, these genes remained activated until the death of the animal. This was in contrast to less dramatic and delayed host immune responses (and less severe disease pathology) in mice infected with influenza viruses containing only subsets of genes from the 1918 virus. These findings indicate a cooperative interaction between the 1918 influenza genes and suggest that enhanced inflammatory and celldeath responses may contribute to severe immunopathology.