Activation of transcription factors NF-kappa B and NF-IL-6 by human immunodeficiency virus type 1 protein R (Vpr) induces interieukin-8 expression

Human immunodeficiency virus (HIV)-positive individuals express elevated le vels of interleukin-8 (IL-8), which is believed to be responsible for some of the clinical manifestations occurring during AIDS. We report here that v irion-derived HIV type 1 (HTV-1) protein R (Vpr) increased IL-8 expression in primary T cells and macrophages, as well as in the T-cell line Jurkat, t he monocytic cell line U937, and the epithelial cell line A549. Vpr appeare d to increase IL-8 expression and IL-8 promoter activity by activating tran scription factors NF-kappa B and NF-IL-6. Elevated Vpr was also shown to in crease transcription of the NF-kappa B and NF-IL-6 enhancer-containing vira l promoters for HIV, cytomegalovirus, and simian virus 40, as well as incre ase the expression of IL-6 and IL-10 in primary macrophages and in A549 cel ls, tumor necrosis factor alpha expression in primary T cells, and IL-6 and gamma interferon expression in U937 cells. These results suggest a new rol e for Vpr in the pathogenesis of HIV infection, namely, the activation of t ranscription factors NF-IL-6 and NF-kappa B.