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, which mediate virus-induced cell fusion, contain two putative amphipathic helical segments with large helical hydrophobic moments near their carboxyl-terminal ends. In an attempt to elucidate the biological role of these amphipathic helical segments, we have synthesized peptides corresponding to residues 768-788 and 826-854 of HIV-1/WMJ-22 gp160. Circular dichroism studies of the peptides showed that the alpha helicity of the peptides increased with the addition of dimyristoyl phosphatidylcholine (DMPC) indicating that the peptides form lipid-associating amphipathic helixes. The peptides solubilized turbid suspensions of DMPC vesicles, and electron microscopy of peptide-DMPC mixtures revealed the formation of discoidal complexes, suggesting that the peptides bind 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 erythrocytes and were found to be toxic to cell cultures. At subtoxic concentrations, the peptides effectively inhibited the fusion of CD4+ cells infected with recombinant vaccinia virus expressing human immunodeficiency virus (HIV)-1 envelope proteins. Based on these results, and reported studies on the mutational analysis of HIV envelope proteins, we suggest that the amphipathic helical segments near the carboxyl terminus of HIV envelope proteins may play a role in lysis of HIV-infected cells and also may modulate the extent of cell fusion observed during HIV infection of CD4+ cells.
Srinivas
S K
SK
Department of Medicine, University of Alabama, Birmingham 35294.
Srinivas
R V
RV
Anantharamaiah
G M
GM
Segrest
J P
JP
Compans
R W
RW
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects; D015686:Gene Products, env / Q000378:metabolism*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism*; D014709:Vero Cells
D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D008081:Liposomes; D010455:Peptides; D011498:Protein Precursors; D004134:Dimyristoylphosphatidylcholine