Glutathione deficiency in HIV infection

Abstract

The tripeptide glutathione (GSH) is the quantitatively most important cysteine derivative of low molecular weight and has numerous important cellular functions. Decreased plasma cysteine and cystine concentrations, decreased intracellular GSH levels, and increased plasma glutamate levels have been found in HIV-infected persons at all stages of the disease and in rhesus macaques within 2 weeks after infection with the closely related simian immunodeficiency virus (SIVmac2). Elevated glutamate levels inhibit the membrane transport of cystine and aggravate thereby the consequences of the cysteine deficiency. Complementary experiments In laboratory animals have shown that glutathione potentiates T cell functions in vivo and in vitro. And studies with healthy human subjects have shown that persons with a combination of a higher than median plasma cystine and lower than median glutamate level have significantly more CD4 T cells than persons with low cystine and high glutamate levels. On the basis of these findings we have proposed that the immunopathology of HIV infection may be largely the consequence of a virus-induced dysregulation of plasma amino acid concentrations. Studies on the mechanistic details revealed that the cysteine and intracellular glutathione deficiency may have several immunologically relevant consequences that affect the antigen presenting cells as well as the responding T lymphocytes. The redox regulation of the transcription factor NFIoB accounts at least for some of the consequences. Biomedical Reviews 1993; 2: 9-13.