Activation of the HIV Type 1 Long Terminal Repeat by X-Irradiation Involves Two Main Rel/NF-κB DNA-Binding Complexes

Abstract

Transcription of human immunodeficiency virus type 1 (HIV-1) is regulated by multiple cis-acting regulatory elements located in the viral long terminal repeats (LTRs). HIV-1 LTR enhancer is activated by a variety of heterologous viral, chemical, and physical agents. Studies have demonstrated that irradiation by X-rays induces transcription under the control of the HIV-1 LTR and that ionizing radiations activate DNA binding of the nuclear transcription factor NF-κB. Using various constructs expressing a reporter gene under the control of complete or deleted LTRs of HIV-1, we evidenced that a sequence located in the U3 region was involved in X-ray activation of the HIV-1 LTR in the human colonic carcinoma cell line HT29. The cis-acting element conferring X-ray responsiveness is indistinguishable from HIV NF-κB tandem repeat binding sites (HIV-1 κB). The present work has examined the effects of X-irradiation on the NF-κB transcription factor. Furthermore, we characterized the subunit composition of the two major nuclear NF-κB complexes that bind HIV-1 κB after X-ray irradiation.