Figure 1.
Pathogenicity of the 1918 pandemic influenza virus in non-human primates.
Taubenberger's group isolated viral genome RNA fragments from formalin-fixed, paraffin-embedded autopsy tissue from victims of the 1918 pandemic and determined the coding sequences of all eight RNA segments of the 1918 pandemic virus. Based on these sequences, a virus bearing all eight RNA segments of the 1918 virus was generated by reverse genetics and its pathogenicity was determined in a non-human primate model. The 1918 virus caused a highly pathogenic respiratory infection in non-human primates that culminated in acute respiratory distress and a fatal outcome. The infected animals mounted an immune response, characterized by dysregulation of the antiviral response, indicating that atypical host innate immune responses may contribute to lethality. The infection of nonhuman primates with the 1918 pandemic virus caused severe damage in the lungs (a), whereas no appreciable lesions were observed in the lungs of animals infected with a contemporary human H1N1 virus (b).
Figure 2.
The role of the HA gene in the pathogenicity of the 1918 virus in mice.
Mice infected with a contemporary human H1N1 influenza virus showed no symptoms. In contrast, a virus possessing the HA gene derived from the 1918 virus in the genetic background of the contemporary human H1N1 virus was lethal to mice.
Figure 3.
The role of the viral RNA polymerase complex in the replication properties of the 1918 virus in ferrets.
The 1918 wild-type virus and a virus possessing the 1918 viral RNA polymerase complex genes (i.e., PA, PB1, PB2, and NP) replicated efficiently in both the upper and lower respiratory tracts of ferrets, whereas the replication of the contemporary human H1N1 virus was restricted to the upper respiratory tract, suggesting a role for the viral RNA polymerase complex in the optimal growth of the 1918 virus in the lower respiratory tract of ferrets. +++, high replicative ability; ++, moderate replicative ability; −, no virus detected.