Gene transfer mediated by influenza virus peptides: The role of peptide sequences

Abstract

Amphipathic peptides resembling the N-terminal influenza hemagglutinin HA-2 sequence were tested in liposome leakage assays, erythrocyte lysis assays and transfection experiments. Dimeric HA-2 peptides INF4DI or INF5 release calcein from PC/Chol (6:4) or PC/PE/Chol/SM (10:3:5:2) liposomes with approx. 100-fold higher efficiency than the peptide GALA. GALA mediates calcein leakage from PC or PS liposomes approx. 5-fold more efficiently than INF4DI or INF5. Incorporation of INF5 or INF7 into transferrin-polylysine/DNA complexes improves gene transfer to cultured human melanoma cells by 100-fold. Modifications of influenza-type peptide sequences such as the replacement of conserved glycines by alanine or substitution of the tryptophans considerably reduce their activity in gene transfer. © CNRS-Gauthier-Villars.