Membrane fusion induced by a lipopeptidic epitope from VP3 capside proteinof hepatitis A virus

Palmitoyl-VP3(110-121) (PVP3) is a synthetic lipopeptide derivative of a co ntinuous epitope from the VP3 capsid protein of hepatitis A virus, and it i s highly immunogenic in vivo. We have investigated the interaction of PVP3 with lipid model membranes of varying surface charge. Binding of PVP3 to an ionic vesicles of PC/SM/PE/PS; (PC) 1-palmitoyl-2-oleoyl-phosphatidylcholin e. (SM) sphingomyelin, (PE) 1,2-dipalmitoyl-phosphatidylethanolamine and (P S) L-alpha -phosphatidyl-L-serine, a composition that mimics the lipid comp onent of natural membranes, was determined by tryptophan fluorescence and q uenching 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 determi ned. PVP3 binds to all three types of vesicles, but it adopts different for ms depending on the electrical charge of the interface. This conclusion is supported by the insertion of PVP3 into lipid monolayers of the same charge s spread at the air-water interface. The bound lipopeptide has membrane-des tabilizing effects in all three vesicle compositions, as demonstrated by le akage of vesicle contents, whereas lipid mixing only occurs in cationic lip osomes. Our results provide useful information for the design of a liposoma l system that promotes a direct delivery of the membrane-incorporated immun ogen to the immunocompetent cells, potentially increasing the immune respon se from the host. Copyright (C) 2001 John Wiley & Sons, Ltd.