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Published on: January 24, 2016

Identification of TRAIL as an interferon regulatory factor 3 transcriptional target

Jessica R Kirshner1, Alla Y Karpova, Maren Kops

  • 1Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Journal of Virology
|July 5, 2005
PubMed

Insights

Paramyxovirus infection triggers apoptosis via interferon regulatory factor 3 (IRF-3). This study reveals IRF-3 upregulates the apoptosis-inducing gene TRAIL, identifying a new mechanism for viral-induced cell death.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Virus-infected cells initiate interferon production and apoptosis to limit viral spread.
  • Paramyxovirus infection induces apoptosis mediated by interferon regulatory factor 3 (IRF-3), but its precise mechanism remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which IRF-3 mediates apoptosis during viral infection.
  • To identify novel transcriptional targets of IRF-3 involved in the apoptosis pathway.

Main Methods:

  • Analysis of IRF-3 involvement in the transcriptional induction of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
  • Investigation of IRF-3 binding to the TRAIL promoter.
  • Measurement of TRAIL and DR5 mRNA levels following viral infection.

Main Results:

  • IRF-3 directly upregulates TRAIL transcription following viral infection.
  • IRF-3 binds to an interferon-stimulated response element (ISRE) in the TRAIL promoter.
  • Both TRAIL and its receptor, DR5, mRNA expression are induced upon viral infection.

Conclusions:

  • TRAIL is identified as a novel transcriptional target of IRF-3.
  • IRF-3 plays a crucial role in inducing apoptosis through TRAIL upregulation during paramyxovirus infection.

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