Human Immunodeficiency Virus Type 1 Tat Protein Activates Transcription Factor NF-kappaB Through the Cellular Interferon-inducible, Double-stranded RNA-dependent Protein Kinase, PKR

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1999 Jul 10

PMID 10400814

Citations 37

Authors

F Demarchi

M I Gutierrez

M Giacca

Affiliations

Soon will be listed here.

Abstract

The transactivator protein of human immunodeficiency virus type 1 (HIV-1) (Tat) is a powerful activator of nuclear factor-kappaB (NF-kappaB), acting through degradation of the inhibitor IkappaB-alpha (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-kappaB 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-kappaB by Tat required integrity of the basic domain of Tat; previous studies have indicated that this domain is necessary for specific Tat-PKR interaction.

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