Role of lentiviral lytic polypeptide I (LLP-I) in the selective cytotoxicity of gamma-glutamylcysteine ethyl ester against human immunodeficiency virus type 1-producing cells.

Selective cytotoxic effects of gamma-glutamylcysteine ethyl ester (gamma-GCE) against human immunodeficiency virus type 1 (HIV-1)-infected H-9 T lymphocytic cells were demonstrated previously. However, the mechanism of those effects remained unclear. Here, we report on enhanced cytotoxicity of the lentiviral lytic peptide I (LLP-I) of gp41, the envelope transmembrane glycoprotein of HIV-1, in the presence of gamma-GCE. Without gamma-GCE, the cytotoxic effect of LLP-I was transient, whereas with gamma-GCE, cell death induced by LLP-I remained continuous until termination. Of note, such effects by gamma-GCE were also observed with another unrelated amphipathic peptide toxin, melittin. These results suggest that the synergistic cytotoxic effect of gamma-GCE and LLP-I may play a central role in the molecular mechanism of the selective cytotoxicity of gamma-GCE in HIV-1-infected T lymphocytic cells.