Department of Bioresources, Hokkaido University Research Center for Zoonosis Control, Kita-ku, Sapporo, Hokkaido, Japan.
PLoS One. 2013;8(2):e55321. doi: 10.1371/journal.pone.0055321. Epub 2013 Feb 8.
Infection of influenza A virus in mammals induces hyper lung pneumonia, which often causes lethal diseases. FasL is a specific ligand of Fas, which is a type-I transmembrane protein to induce cell death. Previously, it has been reported that the hyper induction of gene expression associated with Fas signal is observed in lethal influenza A virus infection. More importantly, it was also reported that functional mutation of the FasL gene protects the host against influenza A virus infection. These observations suggest that induction of FasL signal is functionally associated with the severity of influenza. However, regulation of the induction of FasL or Fas by influenza A virus infection is still unknown. Here, we demonstrated that FasL is induced after the viral infection, and inhibition of the Fas/FasL signal by treatment with a recombinant decoy receptor for FasL (Fas-Fc) increases the survival rate of mice after lethal infection of influenza A virus as well as functional mutation of the FasL gene in gld/gld mice. In addition, the induction level of FasL gene expression in the lung was correlated with the severity of influenza. We also showed that a variety of types of cells in the lung express FasL after the viral infection. Furthermore, type-I interferon induced by the viral infection was shown to be critical for induction of FasL protein expression in the lung. These findings suggested that expression of FasL protein induced by type-I IFN on the lung cell surface is critical to determine the severity of influenza.
流感病毒 A 型在哺乳动物中的感染会导致肺部严重感染，这常常导致致命的疾病。FasL 是 Fas 的特异性配体，Fas 是一种 I 型跨膜蛋白，可诱导细胞死亡。先前已经报道，在致死性流感 A 型病毒感染中观察到与 Fas 信号相关的基因表达的过度诱导。更重要的是，还报道了 FasL 基因的功能突变可保护宿主免受流感 A 型病毒感染。这些观察结果表明，FasL 信号的诱导与流感的严重程度具有功能相关性。然而，流感 A 型病毒感染诱导 FasL 或 Fas 的调节仍不清楚。在这里，我们证明 FasL 在病毒感染后被诱导，并且通过用 FasL（Fas-Fc）的重组诱饵受体处理来抑制 Fas/FasL 信号，可提高感染致死性流感 A 型病毒后小鼠的存活率，以及 gld/gld 小鼠中 FasL 基因的功能突变。此外，肺部 FasL 基因表达的诱导水平与流感的严重程度相关。我们还表明，病毒感染后肺部的各种类型细胞表达 FasL。此外，病毒感染诱导的 I 型干扰素对于诱导肺部 FasL 蛋白表达至关重要。这些发现表明，I 型 IFN 在肺细胞表面诱导的 FasL 蛋白表达对于决定流感的严重程度至关重要。
