The amino-terminal peptide of HIV-1 glycoprotein 41 lyses human erythrocytes and CD4+ lymphocytes.
Functional studies assessed the cytolytic activity of the amino terminal peptide (FP-I; 23 residues 519-541) of the glycoprotein 41,000 (gp41) of the Human Immunodeficiency Virus Type-1 (HIV-1). Synthetically prepared FP-I efficiently hemolyzed human red blood cells at 37 degrees C, with 40% lysis at 32 microM. Kinetic studies indicated that FP-I induced maximal hemolysis in 30 min, probably through tight binding of the peptide with the red cell membrane. The Phe-Leu-Gly-Phe-Leu-Gly (residues 526-531) motif in FP-I apparently plays a critical role in lysis of red cells, since no hemolytic activity was observed for an amino-acid-substituted FP-I in which the unique Phe-Leu-Gly-Phe-Leu-Gly was converted to Ala-Leu-Gly-Ala-Leu-Gly. As neither smaller constituent peptides (e.g., residues 519-524 and residues 526-536) nor a N-terminal flanking peptide (e.g., residues 512-523) induced red cell hemolysis, the entire 23-residue (519-541) sequence of FP-I may be required for hemolytic activity. FP-I was also cytolytic with CD4(+)-bearing Hut-78 cells, with 40% lysis at approx. 150 microM. These results are consistent with an earlier hypothesis that the N-terminal peptide of gp41 may partially contribute to the in vivo cytopathic actions of HIV-1 infection (Gallaher, W.R. (1987) Cell 50, 327-328).
Chemistry Department, California State Polytechnic University, Pomona.
P W
PW
Mobley
C C
CC
Curtain
A
A
Kirkpatrick
M
M
Rostamkhani
A J
AJ
Waring
L M
LM
Gordon
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D016923:Cell Death; D015700:HIV Envelope Protein gp41 / Q000502:physiology*; D006461:Hemolysis; D006801:Humans; D008555:Melitten / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C076451:HIV envelope protein gp41 (519-541); D008555:Melitten