Regulation of Unbalanced Redox Homeostasis Induced by the Expression of Wild-Type HIV-1 Viral Protein R (NL4-3Vpr) in Fission Yeast

Abstract

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 G2 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 (O2·), 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 O2· 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.

Abbreviations

CAT:

catalase

DHR 123:

dihydrorhodamine 123

EPR:

electron paramagnetic resonance

ET:

ethidium bromide

GPx:

glutathione peroxidase

GR:

gluthathione reductase

GSH:

glu-tathione

GSSG:

glutathione disulfde

GST:

gluthatione S-transferase

G6PD:

glucose-6-phosphate dehydrogenase

HIV-1 Vpr:

human immunodefciency virus type-1 viral protein R

NL4-3Vpr:

wild-type Vpr

PBN:

N-tert-butyl-α-phenylnitrone

ROS:

reactive oxygen species

S. pombe:

Schizosaccharomyces pombe

SOD:

superoxide dismutase

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Correspondence to Eszter Virág.

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Gazdag, Z., Stromájer-rácz, T., Belagyi, J. et al. Regulation of Unbalanced Redox Homeostasis Induced by the Expression of Wild-Type HIV-1 Viral Protein R (NL4-3Vpr) in Fission Yeast. BIOLOGIA FUTURA 66, 326–338 (2015). https://doi.org/10.1556/018.66.2015.3.8

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Keywords

  • HIV-1
  • Vpr
  • oxidative stress
  • fission yeast
  • Schizosaccharomyces pombe