Viral IFN-Regulatory factors inhibit activation-induced cell death via two positive regulatory IFN-regulatory factor 1-dependent domains in the CD95 ligand Promoter
The CD95 (also called APO-1/Fas) system plays a major role in the induction of apoptosis in lymphoid and nonlymphoid tissues. The CD95 ligand (CD95L) is induced in response to a variety of signals, including IFN-γ and TCR/CD3 stimulation. Here we report the identification of two positive regulatory...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 1, 2002
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| In: |
The journal of immunology
Year: 2002, Volume: 168, Issue: 3, Pages: 1226-1234 |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.168.3.1226 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.168.3.1226 Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/168/3/1226 
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| Author Notes: | Sabine Kirchhoff, Thorsten Sebens, Sven Baumann, Andreas Krueger, Rainer Zawatzky, Min Li-Weber, Edgar Meinl, Frank Neipel, Bernhard Fleckenstein, and Peter H. Krammer |
| Summary: | The CD95 (also called APO-1/Fas) system plays a major role in the induction of apoptosis in lymphoid and nonlymphoid tissues. The CD95 ligand (CD95L) is induced in response to a variety of signals, including IFN-γ and TCR/CD3 stimulation. Here we report the identification of two positive regulatory IFN-regulatory factor-dependent domains (PRIDDs) in the CD95L promoter and its 5′ untranslated region, respectively. EMSAs demonstrate specific binding of IFN-γ-induced IFN-regulatory factor 1 (IRF-1) to the PRIDD sequences. Ectopic IRF-1 expression induces CD95L promoter activity. Furthermore, we demonstrate that PRIDDs play an important role in TCR/CD3-mediated CD95L induction. Most interestingly, viral IRFs of human herpes virus 8 (HHV8) totally abolish IRF-1-mediated and strongly reduce TCR/CD3-mediated CD95L induction. We demonstrate here for the first time that viral IRFs inhibit activation-induced cell death. Thus, these results demonstrate an important mechanism of HHV8 to modulate the immune response by down-regulation of CD95L expression. Inhibition of CD95-dependent T cell function might contribute to the immune escape of HHV8. |
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| Item Description: | Gesehen am 15.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.168.3.1226 |