Antiviral response by natural killer cells through TRAIL gene induction by IFN-α/β

Kojiro Sato, Shigeaki Hida, Hiroshi Takayanagi, Taeko Yokochi, Nobuhiko Kayagaki, Kazuyoshi Takeda, Hideo Yagita, Ko Okumura, Nobuyuki Tanaka, Tadatsugu Taniguchi, Kouetsu Ogasawara

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229 Citations (Scopus)


Natural killer (NK) cells play an important role in early defense against viral infection. The cytotoxic activity of NK cells is increased by interferon-α/β (IFN-α/β), produced en masse in virally infected cells. However, the mechanism(s) by which IFN-α/β contribute to the NK-cell-mediated antiviral response is not well understood. Here we provide evidence that the cytotoxicity of NK cells is enhanced by IFN-α/β through induction of TNF-related apoptosis-inducing ligand (TRAIL). Isolation and analysis of the murine TRAIL promoter revealed the presence of an IFN-stimulated response element (ISRE), which binds to the transcription factor ISGF3 (interferon stimulated gene factor-3). This promoter is indeed activated by IFN-β in ISGF3-dependent manner. We also show that virally infected cells, but not uninfected cells, are susceptible to TRAIL-mediated cytotoxicity in vitro, and that the TRAIL expressed in NK cells is indeed crucial in limiting virus replication in vivo. Thus, our study reveals a new molecular link between IFN-α/β signaling and activation of NK cells in antiviral response of the host.

Original languageEnglish
Pages (from-to)3138-3146
Number of pages9
JournalEuropean Journal of Immunology
Issue number11
Publication statusPublished - 2001


  • Encephalomyocarditis virus
  • NK cell
  • Type I IFN


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