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

Kirchhoff, S., Sebens, T., Baumann, S., Krueger, A., Zawatzky, R., Min, L. W., et al. (2002). Viral IFN-regulatory factors inhibit activation-induced cell death via two positive regulatory IFN-Regulatory factor 1- dependent domains in the CD95 ligand promoter. Journal of Immunology, 168(3), 1226-1234.

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Kirchhoff, S.1, Autor
Sebens, T.1, Autor
Baumann, S.1, Autor
Krueger, A.1, Autor
Zawatzky, R.1, Autor
Min, L. W.1, Autor
Meinl, E.2, Autor           
Neipel, F.1, Autor
Fleckenstein, B.1, Autor
Krammer, P. H.1, Autor
Affiliations:
1German Canc Res Ctr, Div Immunogenet G0300, Neuenheimer Feld; 280, D-69120 Heidelberg, Germany; German Canc Res Ctr, Div Immunogenet G0300, D-69120 Heidelberg, Germany; German Canc Res Ctr, Tumor Immunol Program, D-69120 Heidelberg, Germany; Max Planck Inst Neurobiol, Dept Neuroimmunol, Martinsried, Germany; Univ Munich, Inst Clin Neuroimmunol, Munich, Germany; Univ Erlangen Nurnberg, Inst Clin & Mol Virol, D-91054 Erlangen, Germany, ou_persistent22              
2Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              

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 Zusammenfassung: 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-gamma 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-gamma-induced IFN- regulatory factor I (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 IPF-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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Sprache(n): eng - English
 Datum: 2002-02-01
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 15199
ISI: 000173429300033
 Art des Abschluß: -

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Titel: Journal of Immunology
  Alternativer Titel : J. Immunol.
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 168 (3) Artikelnummer: - Start- / Endseite: 1226 - 1234 Identifikator: ISSN: 0022-1767