Glutathione homeostasis is disturbed in CD4-positive lymphocytes of HIV-seropositive individuals
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Updated: Oct 29, 2026

Isolation of Exosomes from the Plasma of HIV-1 Positive Individuals
Published on: January 5, 2016
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.
Background:
Numerous in vitro tests have suggested that a disturbed cellular glutathione homeostasis plays an important role in the pathogenesis of human immunodeficiency virus (HIV) infection.
Methods:
Using validated high-performance liquid chromatography (HPLC) methods, glutathione concentrations were determined in plasma and in cytosol of CD4+ lymphocytes and CD14+ cells of HIV-seropositive individuals and healthy control subjects. We measured concentrations of total glutathione, which is the sum of reduced (GSH) and oxidised (GSSG) glutathione and mixed disulphides of which there are two fractions: soluble mixed disulphides (GSSR) and protein bound glutathione (ProSSG). Also, non-protein-bound glutathione was measured, which is the sum of GSH, GSSG and GSSR. Thirty-five healthy control subjects and 35 HIV-infected individuals participated in the study.
Results:
We found that in CD4+ lymphocytes from HIV-seropositive individuals, total glutathione levels were significantly higher than in healthy control subjects, whereas the fraction of non-protein-bound glutathione was not different. This can only be explained by an increase in the protein-bound fraction of glutathione indicating the presence of oxidative stress in CD4+ lymphocytes of HIV-seropositive individuals. Glutathione measurements of cytosol of CD14+ cells and plasma were, however, not compatible with significant increased oxidation. Glutathione precursors (cysteine, cysteinylglycine, glutamylcysteine and homocysteine) and products of lipid peroxidation (thiobarbituric acid-reactive substances) were also measured in plasma and did not differ between healthy control subjects and HIV-seropositive individuals.
Conclusion:
We conclude that the glutathione homeostasis is disturbed in CD4+ lymphocytes of HIV-seropositive individuals. The glutathione redox dysbalance in CD4+ lymphocytes could be important in the pathogenesis of HIV infection and have implications for therapy.
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