Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus
Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus
复制标题
DOI：
10.1038/nature05495
复制
发表时间：
2007-01-18
期刊：
影响因子：
64.8
通讯作者：
Kawaoka, Yoshihiro
中科院分区：
文献类型：
--
作者：
Kobasa, Darwyn;Jones, Steven M.;Kawaoka, Yoshihiro
1918年的流感大流行异常严重，导致全球约5000万人死亡(1)。1918年的病毒在小鼠中也具有高致病性，研究已经确定了小鼠中这种毒性表型的多基因起源（2-4）。然而，这些对1918年病毒的初步描述并没有解决其在灵长类动物中的致病潜力问题。在这里，我们证明1918年病毒引起食蟹猴模型的高致病性呼吸道感染，最终导致急性呼吸窘迫和致命的结果。此外，受感染的动物产生了免疫反应，其特征是抗病毒反应失调，不足以提供保护，这表明非典型宿主先天免疫反应可能导致致命。流感病毒调节宿主免疫反应的能力，如H5N1禽流感病毒所显示的能力(5)，可能是强毒性流感病毒共有的一个特征。
The 1918 influenza pandemic was unusually severe, resulting in about 50 million deaths worldwide(1). The 1918 virus is also highly pathogenic in mice, and studies have identified a multigenic origin of this virulent phenotype in mice(2-4). 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(5), may be a feature shared by the virulent influenza viruses.