Glutathione homeostasis is disturbed in CD4-positive lymphocytes of HIV-seropositive individuals

A J van der Ven1, H J Blom, W Peters

  • 1University Hospital Nijmegen, The Netherlands.

Insights

Glutathione homeostasis is disturbed in CD4+ lymphocytes of HIV-infected individuals, indicating oxidative stress. This redox imbalance in CD4+ cells may impact HIV pathogenesis and treatment strategies.

Area of Science:

  • Biochemistry
  • Immunology
  • Virology

Background:

  • Disturbed cellular glutathione homeostasis is implicated in human immunodeficiency virus (HIV) pathogenesis.
  • In vitro studies suggest a significant role for glutathione imbalance in HIV infection.

Purpose of the Study:

  • To investigate glutathione homeostasis in CD4+ lymphocytes, CD14+ cells, and plasma of HIV-seropositive individuals.
  • To determine if oxidative stress is present in immune cells of HIV-infected individuals.

Main Methods:

  • Validated high-performance liquid chromatography (HPLC) was used to measure total glutathione, reduced glutathione (GSH), oxidized glutathione (GSSG), and mixed disulfides (GSSR, ProSSG) in plasma and cell cytosol.
  • Concentrations of non-protein-bound glutathione and glutathione precursors were also assessed.
  • Study included 35 HIV-seropositive individuals and 35 healthy controls.

Main Results:

  • CD4+ lymphocytes from HIV-seropositive individuals showed significantly higher total glutathione levels compared to controls.
  • An increase in protein-bound glutathione fraction in CD4+ lymphocytes suggests oxidative stress.
  • Glutathione levels in CD14+ cells and plasma did not indicate significant oxidation; plasma precursors and lipid peroxidation products were also unchanged.

Conclusions:

  • Glutathione homeostasis is demonstrably disturbed in CD4+ lymphocytes of individuals with HIV infection.
  • The observed glutathione redox dysbalance in CD4+ lymphocytes is potentially significant for HIV pathogenesis.
  • Findings suggest potential therapeutic implications for managing glutathione levels in HIV treatment.
Abstract

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