The role of blood cell membrane lipids on the mode of action of HIV-1 fusion inhibitor sifuvirtide

© 2010 Elsevier Inc.Sifuvirtide is a gp41 based peptide that inhibits HIV-1 fusion with the host cells and is currently under clinical trials. Previous studies showed that sifuvirtide partitions preferably to saturated phosphatidylcholine lipid membranes, instead of fluid-phase lipid vesicles. We extended the study to the interaction of the peptide with circulating blood cells, by using the dipole potential sensitive probe di-8-ANEPPS. Sifuvirtide decreased the dipole potential of erythrocyte and lymphocyte membranes in a concentration dependent manner, demonstrating its interaction. Also, the lipid selectivity of the peptide towards more rigid phosphatidylcholines was confirmed based on the dipole potential variations. Overall, the interaction of the peptide with the cell membranes is a contribution of different lipid preferences that presumably directs the peptide towards raft-like domains where the receptors are located, facilitating the reach of the peptide to its molecular target, the gp41 in its pre-fusion conformation.This work was funded by Fundação para a Ciência e Tecnologia (FCT) of the Portuguese Ministry of Science, Technology and Higher Education (MCTES), including project PTDC/QUI-BIQ/104787/2008 and Ph.D. Grant SFRH/BD/42205/2007 for P.M.M. The funding source did not have a direct involvement in this study