AEGiS-11IAC: Lipid membrane fusion induced by the human immunodeficiency virus type 1 gp41 N-terminal extremity is determined by its orientation in the lipid bilayer.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

Print this Article


Lipid membrane fusion induced by the human immunodeficiency virus type 1 gp41 N-terminal extremity is determined by its orientation in the lipid bilayer.

Int Conf AIDS 1996 Jul 7-12; 11:6 (abstract no. We.A.156)
Martin I, Schaal H, Scheid A, Ruysschaert JM; U.L.B., LCPMI, Brussels, Belgium.

OBJECTIVE: To analyze the role of the HIV-1 gp41 N-terminal domain in the viral fusogenic activity.

METHODS: IR spectroscopy

RESULTS: The amino-terminal extremity of the HIV-1 transmembrane protein (gp41) is thought to play a pivotal role in the fusion of virus membranes with the plasma membrane of the target cell and in syncytium formation. Peptides with sequences taken from the HIV-1 gp41 fusogenic (synthetic peptides SPwt and SP-2) and non-fusogenic (SP-3 and SP-4) glycoproteins adopt mainly a beta-sheet conformation in the absence of lipid as determined by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), and after interaction with large unilamellar liposomes, the beta-sheet is partly converted into a alpha-helical conformation. Peptides SPwt and SP-2, but not SP-3 and SP-4, were able to promote lipid mixing as assessed by fluorescence energy transfer assay and dye leakage in a vesicle leakage assay. Using polarized ATR-FTIR, SPwt and SP-2 were found to adopt an oblique orientation in the lipid membrane, whereas SP-3 and SP-4 were oriented nearly parallel to the plane of the membrane.

CONCLUSIONS: These findings confirm the correlation between the membrane orientation of the alpha-helix and the lipid mixing ability in vitro. Interestingly, the data provide a direct correlation with the fusogenic activity of the parent glycoproteins in vivo.

Keywords: AEGIS, Membrane Fusion, Lipid Bilayers, HIV-1, Liposomes, Spectroscopy, Fourier Transform Infrared, Molecular Conformation, Peptides, Human, In Vitro, ICA11KWDaegis,membranefusion,lipidbilayers,hiv-1,liposomes,spectroscopy,fouriertransforminfrared,molecularconformation,peptides,human,invitro,ica11

960707
WeA156

Copyright © 1996 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.