Regulation of Unbalanced Redox Homeostasis Induced by the Expression of Wild-Type HIV-1 Viral Protein R (Nl4-3Vpr) in Fission Yeast

The wild-type viral protein R (Vpr) of human immunodeficiency virus type 1 exerts multiple effects on cellular activities during infection, including the induction of cell cycle G 2 arrest and the death of human cells and cells of the fission yeast Schizosaccharomyces pombe . In this study, wild-type Vpr (NL4-3Vpr) integrated as a single copy gene in S. pombe chromosome was used to investigate the molecular impact of Vpr on cellular oxidative stress. NL4-3Vpr triggered an atypical response in early (14-h), and a wellregulated oxidative stress response in late (35-h) log-phase cultures. Specifically, NL4-3Vpr expression induced oxidative stress in the 14-h cultures leading, to decreased levels of superoxide anion (O 2 · − ), hydroxyl radical (·OH) and glutathione (GSH), and significantly decreased activities of catalase, glu-tathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione S-transferase. In the 35-h cultures, elevated levels of O 2 · − and peroxides were accompanied by increased activities of most antioxidant enzymes, suggesting that the Vpr-induced unbalanced redox state of the cells might contribute to the adverse effects in HIV-infected patients.