title: Type-I interferon is critical for FasL expression on lung cells to determine the severity of influenza.
abstract: 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.
authors: Department of Bioresources, Hokkaido University Research Center for Zoonosis Control, Kita-ku, Sapporo, Hokkaido, Japan.
authors: Daisuke
authors: D
authors: Fujikura
authors: Satoko
authors: S
authors: Chiba
authors: Daisuke
authors: D
authors: Muramatsu
authors: Mika
authors: M
authors: Kazumata
authors: Yosuke
authors: Y
authors: Nakayama
authors: Taro
authors: T
authors: Kawai
authors: Shizuo
authors: S
authors: Akira
authors: Hiroshi
authors: H
authors: Kida
authors: Tadaaki
authors: T
authors: Miyazaki
mesh_terms: D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D017931:DNA Primers; D004285:Dogs; D053222:Fas Ligand Protein / Q000378:metabolism*; D005434:Flow Cytometry; D007370:Interferon Type I / Q000502:physiology*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007370:Interferon Type I