Reactive oxygen species activate HIV long terminal repeat via post-translational control of NF-κB

Reduction/oxidation disorder is one of the most common ailments in HIV-infected patients, and such patients are frequently left exposed to chronic oxidative stress after the generation of reactive oxygen species (ROS). Although a variety of clinical trials to inhibit HIV infection have been conducted by focusing on oxidative stress, their precise targets and reaction mechanism have remained unclear. In this study, we demonstrate that H2O2 treatment strongly induced HIV long terminal repeat (LTR)-driven luciferase expression in Jurkat T lymphocytes via NF-κB activation. Treatment with the SN50 peptide or the mutation of NF-κB binding site on LTR resulted in impaired LTR activity in response to ROS. H2O2 induced both IκB degradation and covalent modification of p65. CBP/p300-induced hyperacetylation as well as phosphorylation of p65 was implicated in ROS-mediated LTR activation. The results of our study showed that ROS-induced HIV LTR activation involves immediate early NF-κB activation at the post-translational level.