Reports of the antiviral activity of aliphatic alcohols led us to investigate the effects of aliphatic alcohols, from 10 to 20 carbons in length, on the phase transition behaviour of model phospholipids and on the fusion of influenza to liposomes. Contrary to the effects of many other antiviral agents, we find that alcohols are potent promoters of the inverted hexagonal phase. However, we also find that aliphatic alcohols have little effect on influenza fusion to liposomes. Eicosanol is the only aliphatic alcohol tested which substantially increases in fusion of influenza virus. We also find that long chain alcohols display multi-component bilayer to hexagonal phase transitions at higher mole fractions. This suggests that eicosanol may be facilitating fusion by creating defects between alcohol-rich and alcohol-poor regions of the lipid bilayer.
Abbreviations: IMI, inverted micellar intermediate; ILA, interlamellar attachment; HII, inverted hexagonal phase; Lα, liquid crystalline phase; Lβ, gel phase; Tm, main transition (Lβ to Lα); TH, bilayer to hexagonal phase transition (Lα to HII); HA, influenza hemagglutinin; PC, phosphatidylcholine; PE, phosphatidylethanolamine; DEPE, dieladoylphosphatidylethanolamine; DEPC, dielaidoylphosphatidylcholine; di-PoPE, dipalmitoleoylphosphatidylethanolamine; DOPC, dioleoylphosphatidylcholine; DOPE, dioleoylphosphatidylethanolamine; LUV, large unilamellar vesicle; R18, octadecylrhodamine; DMSO, dimethylsulfoxide; DSC, differential scanning calorimetry