OXIDATIVE STRESS IN HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Infection by the human immunodeficiency virus (HIV-1) causes chronic o ngoing inflammation in HIV-1 seropositive individuals as shown by high plasma levels of inflammatory cytokines and production of reactive ox ygen intermediates (ROIs). One source of ROIs is provided from the ver y early stages of HIV infection by activated polymorphonuclear neutrop hils. Tat, the viral protein. is also specifically responsible for an endogenous cellular increase of ROI. In this review we also evaluate t he effects of this oxidative stress on various biological parameters s uch as immune response and survival of T lymphocytes, virus transcript ion and replication. It was clearly demonstrated in ex vivo experiment s that the oxidative stress due to infection itself participates in CD 4(+) T lymphocyte depletion by increasing their rate of apoptosis and particularly of Fas-induced apoptosis. This oxidative stress also faci litates NF-kappa B-dependent activation of HIV transcription. In vitro studies suggest that the early steps of HIV activation from its quies cent state might be subsequently facilitated by this oxidative environ ment, whereas already active replication is not influenced. The data p resented here lead to a better understanding of the consequences of ox idative stress on the pathophysiology of HIV infection and also enable us to evaluate the potential use of antioxidant molecules as therapeu tic agents against AIDS.