title: Control of baculovirus gp64-induced syncytium formation by membrane lipid composition.
abstract: We have investigated the effects of membrane lipid composition on biological membrane fusion triggered by low pH and mediated by the baculovirus envelope glycoprotein gp64. Lysolipids, either added exogenously or produced in situ by phospholipase A2 treatment of cell membranes, reversibly inhibited syncytium formation. Lysolipids also decreased the baculovirus infection rate. In contrast, oleic and arachidonic acids and monoolein promoted cell-cell fusion. Membrane lipid composition affected pH-independent processes which followed the low-pH-induced change in fusion protein conformation. Inhibition and promotion of membrane fusion by a number of lipids could not be explained by mere binding or incorporation into membranes, but rather was correlated with the effective molecular shape of exogenous lipids. Our data are consistent with the hypothesis that membrane fusion proceeds through highly bent membrane intermediates (stalks) having a net negative curvature. Consequently, inverted cone-shaped lysolipids inhibit and cone-shaped cis-unsaturated fatty acids promote stalk formation and, ultimately, membrane fusion.
authors.affiliation: Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
authors.forename: L
authors.initials: L
authors.lastname: Chernomordik
authors.forename: E
authors.initials: E
authors.lastname: Leikina
authors.forename: M S
authors.initials: MS
authors.lastname: Cho
authors.forename: J
authors.initials: J
authors.lastname: Zimmerberg
mesh_terms: D000818:Animals; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008027:Light; D008244:Lysophosphatidylcholines / Q000378:metabolism / Q000494:pharmacology; D008561:Membrane Fusion / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008563:Membrane Lipids / Q000378:metabolism*; D008854:Microscopy, Electron; D017924:Nucleopolyhedroviruses / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology*; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D018411:Spodoptera; D014760:Viral Fusion Proteins; D014763:Viral Matrix Proteins / Q000502:physiology*
chemical_list: D008244:Lysophosphatidylcholines; D008563:Membrane Lipids; D014760:Viral Fusion Proteins; D014763:Viral Matrix Proteins; D010741:Phospholipases A; D054467:Phospholipases A2