GLUTATHIONE INHIBITS HIV REPLICATION BY ACTING AT LATE STAGES OF THE VIRUS LIFE-CYCLE

We investigated the effect of glutathione on the replication of human immunodeficiency virus (HIV) in chronically infected macrophages, a kn own reservoir of the virus in the body. We found that exogenous GSH st rongly suppresses the production of p24(gag) protein as well as the vi rus infectivity. This is related to a dramatic decrease in both buddin g and release of virus particles from chronically infected cells (eith er macrophages or lymphocytes), together with a selective decrease in the expression of gp120, the major envelope glycoprotein, rich in intr achain disulfide bonds and thus potentially sensitive to the effect of a reducing agent such as GSH. Overall data suggest that GSH can inter fere with late stages of virus replication. This would be in agreement with data obtained in cells exposed to herpesvirus type 1 (a DNA viru s) or to Sendai (an RNA virus), showing that the suppression of virus replication by GSH is related to the selective inhibition of envelope glycoproteins. These results suggest a potential role of GSH in combin ation with other antivirals in the treatment of virus-related diseases .