Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia
Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia
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DOI：
10.1016/j.chom.2007.09.001
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发表时间：
2007-10-01
影响因子：
30.3
通讯作者：
McCullers, Jonathan A.
中科院分区：
文献类型：
--
作者：
McAuley, Julie L.;Hornung, Felicita;McCullers, Jonathan A.
在1918年毁灭性的甲型流感病毒大流行期间，继发性细菌性肺炎经常夺去受害者的生命。人们对导致1918年大流行致命性的病毒因素知之甚少。在这里，我们表明，病毒辅助蛋白PB1-F2的表达增强小鼠原发性病毒感染期间的炎症，并增加继发性细菌性肺炎的频率和严重程度。PB1-F2对细菌性肺炎的引发作用可以通过鼻内递送源自PB1-F2的C-末端部分的合成肽在小鼠中重现。相对于其同基因亲本，经工程改造以表达具有与1918年大流行毒株匹配的编码变化的PB1-F2的流感病毒在小鼠中更具毒性，诱导更多的肺部免疫病理学，并导致更严重的继发性细菌性肺炎。这些发现有助于解释1918年病毒株无与伦比的毒力以及大流行期间致命性肺炎的高发病率。
Secondary bacterial pneumonia frequently claimed the lives of victims during the devastating 1918 influenza A virus pandemic. Little is known about the viral factors contributing to the lethality of the 1918 pandemic. Here we show that expression of the viral accessory protein PB1-F2 enhances inflammation during primary viral infection of mice and increases both the frequency and severity of secondary bacterial pneumonia. The priming effect of PB1-F2 on bacterial pneumonia could be recapitulated in mice by intranasal delivery of a synthetic peptide derived from the C-terminal portion of the PB1-F2. Relative to its isogenic parent, an influenza virus engineered to express a PB1-F2 with coding changes matching the 1918 pandemic strain was more virulent in mice, induced more pulmonary immunopathology, and led to more severe secondary bacterial pneumonia. These findings help explain both the unparalleled virulence of the 1918 strain and the high incidence of fatal pneumonia during the pandemic.