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.
Kubota
S
S
Dorrance H Hamilton Laboratories, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. Satoshi.Kubota@mail.tju.edu
Zhang
H
H
Kitahara
S
S
Pomerantz
R J
RJ
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008555:Melitten / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology
D019380:Anti-HIV Agents; D004151:Dipeptides; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C116049:lentiviral lytic peptide type 1, Human immunodeficiency virus 1; C067744:N-gamma-glutamylcysteine ethyl ester; D008555:Melitten