Viral IFN-Regulatory factors inhibit activation-induced cell death via two positive regulatory IFN-regulatory factor 1-dependent domains in the CD95 ligand Promoter

• Verfasst von: Kirchhoff, Sabine [VerfasserIn]
• Verfasst von: Li-Weber, Min [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: Viral IFN-Regulatory factors inhibit activation-induced cell death via two positive regulatory IFN-regulatory factor 1-dependent domains in the CD95 ligand Promoter
• Verf.angabe: Sabine Kirchhoff, Thorsten Sebens, Sven Baumann, Andreas Krueger, Rainer Zawatzky, Min Li-Weber, Edgar Meinl, Frank Neipel, Bernhard Fleckenstein, and Peter H. Krammer
• E-Jahr: 2002
• Jahr: February 1, 2002
• Umfang: 9 S.
• Teil: volume:168
• Teil: year:2002
• Teil: number:3
• Teil: pages:1226-1234
• Teil: extent:9
• Fussnoten: Gesehen am 15.04.2021
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 2002
• Band/Heft Quelle: 168(2002), 3, Seite 1226-1234
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.168.3.1226
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1755014228

Abstract

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.