Molecular Cloning of a New Interferon-induced Factor That Represses Human Immunodeficiency Virus Type 1 Long Terminal Repeat Expression (*)

  1. Catherine Tissot and
  2. Nadir Mechti(§)
  1. From the (1)Institut de Genetique Moleculaire de Montpellier-UMR 9942, CNRS, BP 5051, 1919 Route de Mende, 34033 Montpellier Cedex 1, France
  1. § To whom correspondence should be addressed:
    Institut de Genetique Moleculaire de Montpellier-UMR 9942, CNRS, BP 5051, 1919 Route de Mende, 34033 Montpellier Cedex 1, France.
    Tel.: 67-61-36-61; Fax: 67-04-02-45.

Abstract

Transcriptional induction of genes is an essential part of the cellular response to interferons. To isolate yet unidentified IFN-regulated genes we have performed a differential screening on a cDNA library prepared from human lymphoblastoid Daudi cells treated for 16 h with human α/β interferon (Hu-α/βIFN). In the course of these studies we have isolated a human cDNA which codes for a protein sharing homology with the mouse Rpt-1 gene; it will be referred as Staf-50 for Stimulated Trans-Acting Factor of 50 kDa. Amino acid sequence analysis revealed that Staf-50 is a member of the Ring finger family and contains all the features of a transcriptional regulator able to initiate a second cascade of gene induction (secondary response). Staf-50 is induced by both type I and type II IFN in various cell lines and down-regulates the transcription directed by the long terminal repeat promoter region of human immunodeficiency virus type 1 in transfected cells. These data are consistent with a role of Staf-50 in the mechanism of transduction of the IFN antiviral action.

Footnotes

  • * This work was supported by grants from the Association pour la Recherche contre le Cancer, the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique, and the Association Nationale pour la Recherche sur le Sida. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    The nucleotide sequence(s) reported in this paper has been submitted to the GenBankGraphic/EMBL Data Bank with accession number(s) X82200.

  • 1 The abbreviations used are:

    IFN

    interferon

    Stat

    signal transducer and activator of transcription

    CMV

    cytomegalovirus

    LTR

    long terminal repeat

    HIV-1

    human immunodeficiency virus type 1

    kb

    kilobase pair(s)

    bp

    base pair(s)

    IM

    intermediate motif.

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