Membrane fusion induced by a lipopeptidic epitope from VP3 capside protein of hepatitis A virus.
Palmitoyl-VP3(110--121) (PVP3) is a synthetic lipopeptide derivative of a continuous epitope from the VP3 capsid protein of hepatitis A virus, and it is highly immunogenic in vivo. We have investigated the interaction of PVP3 with lipid model membranes of varying surface charge. Binding of PVP3 to anionic vesicles of PC/SM/PE/PS; (PC) 1-palmitoyl-2-oleoyl-phosphatidylcholine, (SM) sphingomyelin, (PE) 1,2-dipalmitoyl-phosphatidylethanolamine and (PS) L-alpha-phosphatidyl-L-serine, a composition that mimics the lipid component of natural membranes, was determined by tryptophan fluorescence and quenching experiments. In addition, and given the anionic net charge of the lipopeptide, binding to zwitterionic (PC/SM/PE) and cationic PC/SM/PE/DOTAP (DOTAP) 1,2-dioleoyl-3-trimethylammonium-propane mixtures was also determined. PVP3 binds to all three types of vesicles, but it adopts different forms depending on the electrical charge of the interface. This conclusion is supported by the insertion of PVP3 into lipid monolayers of the same charges spread at the air-water interface. The bound lipopeptide has membrane-destabilizing effects in all three vesicle compositions, as demonstrated by leakage of vesicle contents, whereas lipid mixing only occurs in cationic liposomes. Our results provide useful information for the design of a liposomal system that promotes a direct delivery of the membrane-incorporated immunogen to the immunocompetent cells, potentially increasing the immune response from the host.
Chávez
A
A
Department of Physical Chemistry, School of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
Pujol
M
M
Alsina
M A
MA
Cajal
Y
Y
D002213:Capsid / Q000737:chemistry*; D004735:Energy Transfer; D000939:Epitopes / Q000494:pharmacology*; D006507:Hepatovirus / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry*; D008561:Membrane Fusion / Q000187:drug effects*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
D000939:Epitopes; D008074:Lipoproteins; D014364:Tryptophan