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Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus

机译：使用1918年大流行性病毒的血凝素增强A型流感病毒的毒力

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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).
机译：1918-19年的“西班牙”流感大流行是有史以来最破坏性的传染病暴发。至少有2000万人（1）因疾病而死亡，其特征是异常严重且迅速的临床过程。对1918年流感病毒的几个基因进行完整的测序，使得研究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，这项技术允许完全从克隆的互补DNA产生传染性病毒。因此，为了确定可能与1918年大流行性流感病毒毒力有关的特性，生产了包含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。该菌株的HA支持这种小鼠中适应小鼠的病毒的致病性（4,5）。在这里，我们证明了1918年病毒的HA使小鼠对最近在此宿主中无致病性的人类病毒具有更高的致病性。此外，这些表达1918病毒HA的高毒力重组病毒可以感染整个肺部并诱导高水平的巨噬细胞衍生的趋化因子和细胞因子，从而导致炎症细胞浸润和严重出血，这是原始大流行期间产生的疾病的标志（ 6）。

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