Destabilization and fusion of zwitterionic large unilamellar lipid vesicles induced by a beta-type structure of the HIV-1 fusion peptide

JL Nieva, S Nir, J Wilschut*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

The peptide HIVarg, corresponding to a sequence of 23 amino acid residues at the N-terminus of HIV-1 gp41, has the capacity to induce fusion of large unilamellar vesicles (LUV) consisting of negatively charged or zwitterionic phospholipids. In the present study, we further characterize this destabilization and fusion process using LUV consisting of phosphatidylcholine, phosphatidylethanolamine and cholesterol (molar ratio, 1:1:1). Evidence for fusion includes a demonstration of membrane lipid mixing as well as mixing of aqueous vesicle contents. Kinetic analysis of the overall process of vesicle aggregation and fusion revealed that the rate constant of the fusion step per se increased dramatically with the peptide-to-lipid molar ratio, indicating that the peptide acts as a true fusogen. The peptide caused the release of small molecules (ANTS/DPX), whereas large solutes (FITC-dextran, MWav 19,600) were partly retained. The estimated critical number of peptides per vesicle necessary to release vesicle contents, M = 2-4, indicates that leakage does not involve the formation of classical pores. Infrared spectroscopy of the peptide in the presence of liposomes demonstrated that the equilibrium conformation of the membrane-hound peptide is an antiparallel beta-structure. This finding supports the notion that the HIV fusion peptide in a beta-conformation has the capacity to perturb vesicle bilayers, inducing initial permeabilization and subsequent membrane fusion.

Original languageEnglish
Pages (from-to)165-182
Number of pages18
JournalJournal of Liposome Research
Volume8
Issue number2
Publication statusPublished - 1998

Keywords

  • membrane fusion
  • HIV-1
  • fusion peptide
  • liposome
  • lipid-peptide interaction
  • HUMAN-IMMUNODEFICIENCY-VIRUS
  • MASS-ACTION KINETICS
  • MEMBRANE-FUSION
  • ENVELOPE GLYCOPROTEIN
  • PHOSPHOLIPID-VESICLES
  • INFLUENZA-VIRUS
  • SENDAI VIRUS
  • N-TERMINUS
  • LOW PH
  • LIPOSOMES

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