Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus
Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus
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DOI：
10.1038/nature02951
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发表时间：
2004-10-07
期刊：
影响因子：
64.8
通讯作者：
Kawaoka, Y
中科院分区：
文献类型：
--
作者：
Kobasa, D;Takada, A;Kawaoka, Y
1918年至1919年的“西班牙”流感大流行是有史以来最具破坏性的传染病爆发。至少有2000万人（1）死于这种疾病，其特点是异常严重和快速的临床过程。1918年流感病毒的几个基因的完整测序使得研究由反向遗传学产生的病毒中这些基因编码的蛋白质的功能成为可能，反向遗传学是一种允许完全从克隆的互补DNA产生传染性病毒的技术。因此，为了鉴定1918年大流行性流感A毒株的可能与其异常毒力相关的特性，产生了含有1918年毒株的病毒血凝素（2）（HA）和神经氨酸酶（3）（NA）基因的病毒。该毒株的HA支持小鼠适应性病毒在该动物中的致病性（4，5）。在这里，我们表明，HA的1918年病毒赋予增强的致病性小鼠最近的人类病毒，否则非致病性在这个主机。此外，这些表达1918年病毒HA的高毒力重组病毒可感染整个肺并诱导高水平的巨噬细胞衍生的趋化因子和细胞因子，这导致炎性细胞浸润和严重出血，这是最初大流行期间产生的疾病的标志（6）。
The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people(1) died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA. Thus, to identify properties of the 1918 pandemic influenza A strain that might be related to its extraordinary virulence, viruses were produced containing the viral haemagglutinin(2) (HA) and neuraminidase(3) (NA) genes of the 1918 strain. The HA of this strain supports the pathogenicity of a mouse-adapted virus in this animal(4,5). Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host. Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA could infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which resulted in infiltration of inflammatory cells and severe haemorrhage, hallmarks of the illness produced during the original pandemic(6).