MEMBRANE INTERACTIONS OF SYNTHETIC PEPTIDES CORRESPONDING TO AMPHIPATHIC HELICAL SEGMENTS OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN

The human and simian immunodeficiency virus envelope glycoproteins, wh ich mediate virus-induced cell fusion, contain two putative amphipathi c helical segments with large helical hydrophobic moments near their c arboxyl-terminal ends. In an attempt to elucidate the biological role of these amphipathic helical segments, we have synthesized peptides co rresponding to residues 768-788 and 826-854 of HIV-1/WMJ-22 gp160. Cir cular dichroism studies of the peptides showed that the alpha helicity of the peptides increased with the addition of dimyristoyl phosphatid ylcholine (DMPC) indicating that the peptides form lipid-associating a mphipathic helixes. The peptides solubilized turbid suspensions of DMP C vesicles, and electron microscopy of peptide-DMPC mixtures revealed the formation of discoidal complexes, suggesting that the peptides bin d to and perturb lipid bilayers. The peptides were found to lyse lipid vesicles and caused carboxyfluorescein leakage from dye-entrapped egg phosphatidylcholine liposomes. The peptides also lysed human erythroc ytes and were found to be toxic to cell cultures. At subtoxic concentr ations, the peptides effectively inhibited the fusion of CD4+ cells in fected with recombinant vaccinia virus expressing human immunodeficien cy virus (HIV)-1 envelope proteins. Based on these results, and report ed studies on the mutational analysis of HIV envelope proteins, we sug gest that the amphipathic helical segments near the carboxyl terminus of HIV envelope proteins may play a role in lysis of HIV-infected cell s and also may modulate the extent of cell fusion observed during HIV infection of CD4+ cells.