Sphingolipid-dependent fusion of Semliki Forest virus with cholesterol-containing liposomes requires both the 3-hydroxyl group and the double bond of the sphingolipid backbone.
Low-pH-induced membrane fusion of Semliki Forest virus (SFV) in a model system is mediated by sphingolipids in the target membrane; ceramide is the sphingolipid minimally required (J. L. Nieva, R. Bron, J. Corver, and J. Wilschut, EMBO J. 13:2797-2804, 1994). Here, using various ceramide analogs, we demonstrate that sphingolipid-dependent fusion of SFV with cholesterol-containing liposomes exhibits remarkable molecular specificity, the 3-hydroxyl group and the 4,5-trans carbon-carbon double bond of the sphingosine backbone being critical for the sphingolipid to mediate the process. This observation supports the notion that sphingolipids act as a cofactor in SFV fusion, interacting directly with the viral fusion protein to induce its ultimate fusion-active conformation.
Corver
J
J
Department of Physiological Chemistry, Groningen Institute for Drug Studies, University of Groningen, The Netherlands.
Moesby
L
L
Erukulla
R K
RK
Reddy
K C
KC
Bittman
R
R
Wilschut
J
J
D002518:Ceramides / Q000737:chemistry / Q000502:physiology; D002784:Cholesterol / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D008081:Liposomes / Q000737:chemistry; D008561:Membrane Fusion / Q000502:physiology*; D008954:Models, Biological; D015394:Molecular Structure; D011487:Protein Conformation; D012672:Semliki forest virus / Q000502:physiology*; D013107:Sphingolipids / Q000737:chemistry / Q000502:physiology*; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000502:physiology
D002518:Ceramides; D008081:Liposomes; D013107:Sphingolipids; D014760:Viral Fusion Proteins; D002784:Cholesterol