The amino-terminal peptide of HIV-1 glycoprotein 41 lyses human erythrocytes and CD4 + lymphocytes

Abstract

Functional studies assessed the cytolytic activity of the amino-terminal peptide (FP-I; 23 residues 519–541) of the glycoprotein 41000 (gp41) of the Human Immunodeficiency Virus Type-1 (HIV-1). Synthetically prepared FP-I efficiently hemolyzed human red blood cells at 37°C, with 40% lysis at 32 μM. 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 μM. 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).