The amino-terminal peptide of HIV-1 glycoprotein 41 fuses human erythrocytes.
The ability of synthetic peptides based on the amino-terminus of HIV-1 glycoprotein 41,000 (gp41) to fuse human erythrocytes was investigated. Previous site-directed mutagenesis studies have shown an important role for the N-terminal gp41 domain in HIV-fusion, in which replacement of hydrophobic amino acids with polar residues inhibits viral infection and syncytia formation. Here, a synthetic peptide (FP; 23 amino acid residues 519-541) corresponding to the N-terminus of HIV-1 gp41, and also a FP analog (FP526L/R) with Arg replacing Leu-526, were prepared with solid phase techniques. The lipid mixing and leakage of resealed ghosts triggered by these peptides were examined with fluorescence quenching techniques. Peptide-induced aggregation of human erythrocytes was studied using Coulter counter sizing and scanning electron microscopy (SEM). Using resealed erythrocyte ghosts at physiologic pH, FP induces rapid lipid mixing between red cell membranes at doses previously shown to hemolyze intact cells. FP also causes leakage from resealed ghosts, and promotes the formation of multicelled aggregates with whole erythrocytes. Contrarily, similar FP526L/R concentrations did not induce red cell lysis, lipid mixing, leakage or aggregation. Since the fusogenic potency of FP and FP526L/R parallels earlier gp41 mutagenesis studies showing that substitution of Arg for Leu-526 blocks fusion activity, these data suggest that the N-terminal gp41 domain in intact HIV participates in fusion.
Mobley
P W
PW
Chemistry Department, California State Polytechnic University, Pomona, USA.
Lee
H F
HF
Curtain
C C
CC
Kirkpatrick
A
A
Waring
A J
AJ
Gordon
L M
LM
D004903:Erythrocyte Aggregation / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*
D015700:HIV Envelope Protein gp41; D010455:Peptides