FUSION BETWEEN ENVELOPED VIRUSES AND ERYTHROCYTE-MEMBRANES IS INDUCEDBY THE ISOPREINOID ALKANE PRISTANE (2,6,10,14-TETRAMETHYLPENTADECANE)

Pristane (2,6,10,14-tetramethylpentadecane) is an isoprenoid alkane th at induces plasma cell tumors in mice. Infection with certain retrovir uses accelerates tumorigenesis but the nature of the cooperation betwe en pristane and viruses is unknown. The purpose of this study was to i nvestigate the potential influence of pristane on the fusion between e nveloped viruses and mammalian plasma membranes. Using a fluorescence dequenching assay, we found that micromolar amounts of pristane induce d fusion between erythrocyte membranes and both vesicular stomatitis v irus and influenza virus. Induction of fusion occurred with as little as 5 mu M pristane and reached saturation at roughly 50 mu M alkane. C ontrol experiments revealed that induction of fluorescence dequenching was not due to extraneous phenomena such as lipid transfer or non-spe cific interactions with the carrier for pristane (P-cyclodextrin). Fus ion was also induced by standard protocols which involve lowering the pH of the incubation medium. In the presence of pristane, low pH-trigg ered fusion was enhanced. The extent to which pristane induced fusion was dependent upon the orientation of the lipids in the target membran e. That is, fusion was most effective with erythrocyte ghosts which ha d a symmetric lipid distribution and was less effective with ghosts in which the native lipid asymmetry was maintained. Intact erythrocytes, which have an asymmetric lipid distribution, were the least effective targets. This result exactly parallels the pattern observed with acid -induced fusion. Similar patterns were also observed in the temperatur e dependence of fusion induced by these two protocols. The novel fusog enic activity of pristane is discussed with regard to current models o f virus/membrane fusion.