Abstract
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.
MeSH Terms
Ceramides/chemistry,physiology
Cholesterol/chemistry
Hydrogen-Ion Concentration
Hydroxylation
Liposomes/chemistry
Membrane Fusion/physiology
Models, Biological
Molecular Structure
Protein Conformation
Semliki forest virus/physiology
Sphingolipids/chemistry,physiology
Viral Fusion Proteins/chemistry,physiology
Chemicals
Ceramides
Liposomes
Sphingolipids
Viral Fusion Proteins
Cholesterol
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Corver J
Department of Physiological Chemistry, Groningen Institute for Drug Studies, University of Groningen, The Netherlands.
Moesby L
Erukulla R K
Reddy K C
Bittman R
Wilschut J
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