Mitochondrial membrane potential and apoptosis of blood mononuclear cells in untreated HIV-1 infected patients

Abstract

Objectives: Infection with HIV leads to progressive CD4 T-cell loss, resulting in AIDS. Apoptosis is the main mechanism for the loss of infected and bystander cells, but the complex interacting factors inducing and inhibiting apoptosis are not fully understood. Mitochondrial dysfunction is a pivotal step of the apoptotic cascade and can result in reduced mitochondrial membrane potential.

Methods: The mitochondrial membrane potential of peripheral blood mononuclear cells (PBMC) was measured by flow cytometry using the dye JC-1 (Molecular Probes Inc). Apoptotic cells were identified using the Annexin V assay (Becton Dickinson GmbH).

Results: The mitochondrial membrane potential of PBMC was significantly decreased and apoptotic cell rate was increased in HIV-infected therapy-naïve patients compared with HIV-negative controls. There was a highly significant correlation between the mitochondrial membrane potential and the rate of apoptosis. CD4 cell count was correlated negatively to the apoptotic rate and positively to the mitochondrial membrane potential.

Conclusions: The JC-1 assay is a sensitive tool to detect changes of mitochondrial membrane potential associated with apoptosis in HIV-infected therapy-naïve patients. We could show in vivo that a reduction of mitochondrial membrane potential is correlated to apoptosis of PBMC, CD4 cell count and HIV viral load during HIV infection.