HIV-TAT PROTEIN ACTIVATES C-JUN N-TERMINAL KINASE AND ACTIVATOR PROTEIN-1

Human immunodeficiency virus-P tat (HIV-tat) protein, like other proin flammatory cytokines (such as TNF), activates a wide variety of cellul ar responses, some of which play a critical role in progression of HIV infection. Whether HIV-tat, like TNF, also activates c-Jun N-terminal kinase (JNK) and the transcription factor activator protein (AP)-1 is not known. We show that treatment of human histiocytic lymphoma U937 cells with the HIV-tat protein causes activation of JNK and AP-1 in a time- and dose-dependent manner, Transfection of a T cell line, H9 cel ls with the HIV-tat gene also resulted in an activation of JNK that wa s not further increased by treatment of cells with exogenous HIV-tat p rotein, Neutralizing Ab against HN-tat inhibited the HIV-tat-mediated JNK activation. The activation of JNK by HIV-tat appears to be mediate d through generation of free radical species, since pretreatment of ce lls with N-acetylcysteine (NAC) abolished the effect. Overall our resu lts demonstrate that HIV-tat activates JNK and AP-P, which may contrib ute to the pathogenesis of AIDS.