Oxidative stress induced by HIV-1 F34IVpr in Schizosaccharomyces pombe is one of its multiple functions

Abstract Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) exerts multiple effects on viral and host cellular activities during infection, including induction of cell cycle G 2 arrest and cell death in both human and the fission yeast Schizosaccharomyces pombe cells. In this study, a mutant derivative of Vpr (F34IVpr), which causes transitent G 2 arrest with little or no effect of cell killing, was used to study the molecular impact of Vpr on cellular oxidative stress responses in S. pombe . We demonstrated here that F34IVpr triggers low level of complex and atypical oxidative stress responses in comparison with its parental strain SP223 in early (14-h) and late (35-h) log phase cultures. Specifically, F34IVpr production in S. pombe causes significantly elevated levels of reactive oxygen species such as superoxide and peroxides; meanwhile, it also induces decreased levels of glutathione, hydroxyl radical concentrations and specific enzyme activities such as those of antioxidant enzymes including superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione transferase. These observations may provide functional insights into the significance of Vpr-induced oxidative stress as part of the multifaceted functions of Vpr, and contribute to the development of future new strategies aimed to reduce the adverse Vpr-mediated effects in HIV-infected patients.