Human immunodeficiency virus type 1 Tat protein activates transcription factor NF-kappa B through the cellular interferon-inducible, double-stranded RNA-dependent protein kinase, PKR

The transactivator protein of human immunodeficiency virus type I (HIV-1) ( Tat) is a powerful activator of nuclear factor-KB (NF-kappa B), acting thro ugh degradation of the inhibitor I kappa B-alpha (F. Demarchi, F. d'Adda di Fagagna, A. Falaschi, and Mt Giacca, J. Virol. 70:4427-4437, 1996). Here, we show that this activity of Tat requires the function of the cellular int erferon-inducible protein kinase PKR, Tat-mediated NF-kappa B activation an d 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 d ominant-negative mutant of PKR specifically reduced the levels of Tar trans activation in different human cell types. Activation of NF-kappa B by Tat r equired integrity of the basic domain of Tat; previous studies have indicat ed that this domain is necessary for specific Tat-PKR interaction.