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

Research output: Contribution to journalArticlepeer-review

694 Scopus citations

Abstract

The 1918 influenza pandemic was unusually severe, resulting in about 50 million deaths worldwide. The 1918 virus is also highly pathogenic in mice, and studies have identified a multigenic origin of this virulent phenotype in mice. However, these initial characterizations of the 1918 virus did not address the question of its pathogenic potential in primates. Here 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. Furthermore, infected animals mounted an immune response, characterized by dysregulation of the antiviral response, that was insufficient for protection, indicating that atypical host innate immune responses may contribute to lethality. The ability of influenza viruses to modulate host immune responses, such as that demonstrated for the avian H5N1 influenza viruses, may be a feature shared by the virulent influenza viruses.

Original languageEnglish (US)
Pages (from-to)319-323
Number of pages5
JournalNature
Volume445
Issue number7125
DOIs
StatePublished - Jan 18 2007

ASJC Scopus subject areas

  • General

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