Fusion between enveloped viruses and erythrocyte membranes is induced by the isoprenoid alkane pristane (2,6,10,14-tetramethylpentadecane).
Pristane (2,6,10,14-tetramethylpentadecane) is an isoprenoid alkane that induces plasma cell tumors in mice. Infection with certain retroviruses accelerates tumorigenesis but the nature of the cooperation between pristane and viruses is unknown. The purpose of this study was to investigate the potential influence of pristane on the fusion between enveloped viruses and mammalian plasma membranes. Using a fluorescence dequenching assay, we found that micromolar amounts of pristane induced fusion between erythrocyte membranes and both vesicular stomatitis virus and influenza virus. Induction of fusion occurred with as little as 5 microM pristane and reached saturation at roughly 50 microM alkane. Control experiments revealed that induction of fluorescence dequenching was not due to extraneous phenomena such as lipid transfer or non-specific interactions with the carrier for pristane (beta-cyclodextrin). Fusion was also induced by standard protocols which involve lowering the pH of the incubation medium. In the presence of pristane, low pH-triggered fusion was enhanced. The extent to which pristane induced fusion was dependent upon the orientation of the lipids in the target membrane. That is, fusion was most effective with erythrocyte ghosts which had 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 temperature dependence of fusion induced by these two protocols. The novel fusogenic activity of pristane is discussed with regard to current models of virus/membrane fusion.
Janz
S
S
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Shacter
E
E
Herrmann
A
A
D055592:Biophysical Phenomena; D001703:Biophysics; D002273:Carcinogens / Q000633:toxicity*; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000187:drug effects; D007700:Kinetics; D008561:Membrane Fusion / Q000187:drug effects*; D008563:Membrane Lipids / Q000737:chemistry; D010954:Plasmacytoma / Q000139:chemically induced; D013050:Spectrometry, Fluorescence; D013696:Temperature; D013729:Terpenes / Q000633:toxicity*; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D002273:Carcinogens; D008563:Membrane Lipids; D013729:Terpenes; C009042:pristane