E-TABM-181 - Transcription profiling of bronchus from macaques infected with either the 1918 influenza virus or a humanized contemporary H1N1 influenza virus
Released on 18 January 2007, last updated on 2 May 2014
The 1918 influenza pandemic was unusually severe, resulting in about 50 million deaths worldwide. A reconstructed version of the 1918 (H1N1) virus has been shown to also highly pathogenic in mice; however, the potential virulence and pathogenicity of the 1918 virus in nonhuman primates in unknown. In these studies, we demonstrate that the 1918 virus caused a highly pathogenic respiratory infection in a cynomolgus macaque model that culminated in acute respiratory distress and a fatal outcome. To characterize the global gene expression host response, oligonulceotide microarray analysis was performed on RNA isolated from the bronchus of macaques infected with either the 1918 virus or a humanized contemporary H1N1 influenza virus (A/Kawasaki/173/01). These experiments showed that infected animals mounted an immune response, characterized by dysregulation of the antiviral response, that was insufficient for protection, suggesting that atypical host innate immune responses may contribute to lethality.
transcription profiling by array, co-expression, disease state, time series
Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Darwyn Kobasa, Steven M. Jones, Kyoko Shinya, John C. Kash, John Copps, Hideki Ebihara, Yasuko Hatta, Jin Hyun Kim, Peter Halfmann, Masato Hatta, Friederike Feldmann, Judie B. Alimonti, Lisa Fernando, Yan Li, Michael G. Katze, Heinz Feldmann, Yoshihiro Kawaoka. Nature 445:319-323 (2007)