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Journal of Virology, June 2003, p. 7113-7119, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.7113-7119.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Impairment of Interferon-Induced IRF-7 Gene Expression due to Inhibition of ISGF3 Formation by Trichostatin A

Pierre Génin, Pierre Morin, and Ahmet Civas*

UPR 2228-CNRS, Laboratoire de Régulation Transcriptionnelle et Maladies Génétiques, UFR Biomédicale des Saints-Pères, Université Paris V, 75270 Paris Cedex 06, France

Received 20 December 2002/ Accepted 24 March 2003

Two members of the signal transducer and activator of transcription family, STAT1 and STAT2, form, together with interferon regulatory factor 9 (IRF-9), the ISGF3 complex that activates the expression of the interferon-stimulated genes (ISG). The ISGF3 complex also participates in the virus-induced alpha/beta interferon (IFN-{alpha}/ß) gene amplification cascade by up-regulating IRF-7 gene expression. Here, we show that treatment of cells with trichostatin A (TSA), a deacetylase inhibitor, inhibits the virus-induced activation of IFN-{alpha}/ß promoters and dramatically reduces the ability of different ISG promoters to respond to IFN stimulation. Impairment of IFN-{alpha}/ß and ISG expression by TSA in infected cells is due to the blockage of interferon-stimulated ISGF3 complex formation, which leads to the abolition of IRF-7 gene expression. We also show that the TSA-dependent inhibition of ISGF3 is related to impaired nuclear accumulation of STAT2. Our data suggest that an acetylation/deacetylation mechanism participates in the regulation of cellular distribution and function of STAT2 in IFN-{alpha}/ß signaling.

* Corresponding author. Mailing address: UPR 2228-CNRS, Laboratoire de Régulation Transcriptionnelle et Maladies Génétiques, UFR Biomédicale des Saints-Pères, Université Paris V, 45, rue des Saints-Pères, 75270 Paris Cedex 06, France. Phone: 33-1-42-86-22-84. Fax: 33-1-42-86-20-42. E-mail: civas{at}biomedicale.univ-paris5.fr.

Journal of Virology, June 2003, p. 7113-7119, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.7113-7119.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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