TY - JOUR
T1 - Differential effects of IκB molecules on tat-mediated transactivation of HIV-1 LTR
AU - Harhaj, Edward
AU - Blaney, Joseph
AU - Millhouse, Scott
AU - Sun, Shao Cong
N1 - Funding Information:
We acknowledge Drs. W. C. Greene, A. D. Frankel, and S. Ghosh for providing us the cDNA expression vectors. This work is supported in part by a National Foundation For Infectious Diseases Young Investigator Matching Grant and by Public Health Service Grant 1 R01 CA68471-01 to S.-C.S. S.-C.S. is a scholar of the American Foundation for AIDS Research.
PY - 1996/2/1
Y1 - 1996/2/1
N2 - The tat gene product of the human immunodeficiency virus type 1 (HIV-1) strongly induces the transcription directed by the viral long terminal repeat (LTR). Tat acts by interacting with a target RNA element located immediately downstream of the initiation site. In addition, the action of Tat appears to be assisted by the upstream DNA enhancer elements, including the binding sites for the NF-κB/Rel family of host transcription factors. In the present study, we demonstrate that Tat transactivation of the HIV-1 LTRis markedly inhibited by several cytoplasmic inhibitors of NF-κB/Rel, suggesting the critical involvement of these host transcription factors in the function of the viral Tat protein. Furthermore, the various NF-κB inhibitors appear to have differential effects on Tat. While IκBα, IκBβ, and p100 potently inhibit Tat-mediated transactivation, p105 fails to inhibit, but even moderately synergizes, the action of Tat. We further demonstrate that the action of these NF-κB/Rel inhibitors on Tat correlates with their inhibitory activities on the RelA subunit of NF-κB. Finally, we show that a degradation-resistant IκBα mutant is able to potently inhibit Tat-mediated activation of the HIV-1 LTR in both untreated and tumor necrosis factor α-stimulated T cells, thus suggesting that such an IκBα mutant may serve as a constitutive repressor of HIV-1 LTR
AB - The tat gene product of the human immunodeficiency virus type 1 (HIV-1) strongly induces the transcription directed by the viral long terminal repeat (LTR). Tat acts by interacting with a target RNA element located immediately downstream of the initiation site. In addition, the action of Tat appears to be assisted by the upstream DNA enhancer elements, including the binding sites for the NF-κB/Rel family of host transcription factors. In the present study, we demonstrate that Tat transactivation of the HIV-1 LTRis markedly inhibited by several cytoplasmic inhibitors of NF-κB/Rel, suggesting the critical involvement of these host transcription factors in the function of the viral Tat protein. Furthermore, the various NF-κB inhibitors appear to have differential effects on Tat. While IκBα, IκBβ, and p100 potently inhibit Tat-mediated transactivation, p105 fails to inhibit, but even moderately synergizes, the action of Tat. We further demonstrate that the action of these NF-κB/Rel inhibitors on Tat correlates with their inhibitory activities on the RelA subunit of NF-κB. Finally, we show that a degradation-resistant IκBα mutant is able to potently inhibit Tat-mediated activation of the HIV-1 LTR in both untreated and tumor necrosis factor α-stimulated T cells, thus suggesting that such an IκBα mutant may serve as a constitutive repressor of HIV-1 LTR
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U2 - 10.1006/viro.1996.0062
DO - 10.1006/viro.1996.0062
M3 - Article
C2 - 8615004
AN - SCOPUS:0029669994
SN - 0042-6822
VL - 216
SP - 284
EP - 287
JO - Virology
JF - Virology
IS - 1
ER -