Kobasa Darwyn, Jones Steven M, Shinya Kyoko, Kash John C, Copps John, Ebihara Hideki, Hatta Yasuko, Kim Jin Hyun, Halfmann Peter, Hatta Masato, Feldmann Friederike, Alimonti Judie B, Fernando Lisa, Li Yan, Katze Michael G, Feldmann Heinz, Kawaoka Yoshihiro
Respiratory Viruses, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
Nature. 2007 Jan 18;445(7125):319-23. doi: 10.1038/nature05495.
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.
1918年的流感大流行异常严重，导致全球约5000万人死亡。1918年的病毒对小鼠也具有高度致病性，并且研究已经确定了这种病毒在小鼠中具有多基因起源的毒力表型。然而，对1918年病毒的这些初步特征描述并未解决其在灵长类动物中的致病潜力问题。在此，我们证明1918年病毒在食蟹猴模型中引起了高度致病性的呼吸道感染，最终导致急性呼吸窘迫和致命后果。此外，受感染的动物产生了一种免疫反应，其特征是抗病毒反应失调，不足以提供保护，这表明非典型的宿主固有免疫反应可能导致致死性。流感病毒调节宿主免疫反应的能力，如禽流感H5N1病毒所表现出的那样，可能是致病性流感病毒共有的一个特征。
