Human Immunodeficiency Virus Type 1 Tat Protein Activates Transcription Factor NF-κB through the Cellular Interferon-Inducible, Double-Stranded RNA-Dependent Protein Kinase, PKR

• DOI: 10.1128/jvi.73.8.7080-7086.1999
• Publication Date: 2019-12-31T18:41:02Z
• Authors: Francesca Demarchi; Maria Ines Gutierrez; Mauro Giacca
• Keywords: Protein kinase R; EIF-2 kinase

ABSTRACT The transactivator protein of human immunodeficiency virus type 1 (HIV-1) (Tat) is a powerful activator nuclear factor-κB (NF-κB), acting through degradation the inhibitor IκB-α (F. Demarchi, F. d’Adda di Fagagna, A. Falaschi, and M. Giacca, J. Virol. 70:4427–4437, 1996). Here, we show that this activity Tat requires function cellular interferon-inducible kinase PKR. Tat-mediated NF-κB activation transcriptional induction HIV-1 long terminal repeat were impaired in murine cells which PKR gene was knocked out. Both functions restored by cotransfection with cDNA for Expression dominant-negative mutant specifically reduced levels transactivation different cell types. Activation required integrity basic domain Tat; previous studies have indicated necessary specific Tat-PKR interaction.