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Journal of Virology, August 1999, p. 7080-7086, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Human Immunodeficiency Virus Type 1 Tat Protein Activates
Transcription Factor NF-
B through the Cellular
Interferon-Inducible, Double-Stranded RNA-Dependent Protein
Kinase, PKR
Francesca
Demarchi,1
Maria Ines
Gutierrez,1 and
Mauro
Giacca1,2,*
Molecular Medicine Laboratory, International
Centre for Genetic Engineering and Biotechnology, 34012 Trieste,1 and Istituto di Genetica
Biochimica ed Evoluzionistica del CNR, 27100 Pavia,2 Italy
Received 19 January 1999/Accepted 7 May 1999
The transactivator protein of human immunodeficiency virus type 1 (HIV-1) (Tat) is a powerful activator of nuclear factor-
B (NF-
B),
acting through degradation of the inhibitor I
B-
(F. Demarchi, F. d'Adda di Fagagna, A. Falaschi, and M. Giacca, J. Virol.
70:4427-4437, 1996). Here, we show that this activity of Tat requires
the function of the cellular interferon-inducible protein kinase PKR.
Tat-mediated NF-
B activation and transcriptional induction of the
HIV-1 long terminal repeat were impaired in murine cells in which the
PKR gene was knocked out. Both functions were restored by
cotransfection of Tat with the cDNA for PKR. Expression of a
dominant-negative mutant of PKR specifically reduced the levels of Tat
transactivation in different human cell types. Activation of NF-
B by
Tat required integrity of the basic domain of Tat; previous studies
have indicated that this domain is necessary for specific Tat-PKR interaction.
*
Corresponding author. Mailing address: Molecular
Medicine Laboratory, ICGEB, Padriciano, 99, 34012 Trieste, Italy.
Phone: 390-40-3757.324. Fax: 390-40-226555. E-mail:
giacca{at}icgeb.trieste.it.
Journal of Virology, August 1999, p. 7080-7086, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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