In vitro HIV-1 infection induced a significant decrease in intracellul
ar reduced glutathione (GSH) in human macrophages, Such a decrease was
observed at the time of infection corresponding to maximum release of
virus from infected cells and was not related to cell cytotoxicity, G
SH loss was not related to its oxidation or leakage through the cell m
embrane, Inhibition of intracellular GSH synthesis by buthionine sulfo
ximine (BSO) did not further decrease GSH levels with respect to the d
ecrease caused by HIV alone. However, treatment of macrophages with BS
O significantly increased the HIV yield in the supernatant. Exogenous
GSH strongly suppressed the production of p24 gag protein as well as t
he virus infectivity. Previous observations with other RNA and DNA vir
uses consistently showed that GSH antiviral effect occurred at late st
ages of virus replication and was related to the selective decrease of
specific glycoproteins, such as gp120, which are particularly rich in
disulfide bonds.