LIPOPHOSPHOGLYCAN OF LEISHMANIA-DONOVANI INHIBITS LIPID VESICLE FUSION INDUCED BY THE N-TERMINAL EXTREMITY OF VIRAL FUSOGENIC SIMIAN IMMUNODEFICIENCY VIRUS PROTEIN

Lipophosphoglycan (LPG), the major glycoconjugate of Leishmania parasi tes, was recently shown to be a potent inhibitor of viral infection. T he mechanism by which this natural membrane amphiphile compound inhibi ts membrane fusion was investigated in this study using a simple model membrane system and a synthetic peptide corresponding to the fusion p eptide of simian immunodeficiency virus (SIV). At low concentration (< 10 mu M), LPG inhibits SIV-induced lipid mixing of large unilamellar v esicles composed of an equimolar mixture of egg phosphatidylcholine an d egg phosphatidylethanolamine. Importantly, this inhibition was obser ved regardless of which LPG was inserted in the inner monolayer, the o uter monolayer or both sides of the membrane, suggesting that the inne r monolayer plays a determining role in membrane fusion. Fourier trans form infrared spectroscopy revealed that LPG induced a conformational change of SIV fusion peptide without affecting its capacity to interac t with the lipid membrane. This structural change was shown not to dep end on the LPG localization and was observed even when LPG was exclusi vely associated to the inner lipid membrane.