How lysophosphatidylcholine inhibits cell-cell fusion mediated by the envelope glycoprotein of human immunodeficiency virus.

We have investigated the effect of lysophosphatidylcholine (LPC) on fusion of cells expressing the envelope glycoprotein of HIV-1, gp120/gp41, with cells expressing the receptor for this virus, CD4. Fusion was inhibited by micromolar concentrations of LPC added from an aqueous stock solution, but not by membrane-associated LPC or LPC produced in the membrane by the action of phospholipase A2. No inhibition was found for LPCs with acyl chain lengths shorter than 12 carbon atoms, and the inhibitory effect of longer molecules increased with their length. gp120-CD4 specific cell-cell binding was inhibited with a chain length dependence corresponding to that of fusion, but with palmitoyl-LPC, fusion was more strongly affected than binding. These data indicate that gp120/gp41-induced fusion is inhibited by LPC because LPC affects viral protein-host cell binding and not because LPC prevented the formation of lipid intermediates required for fusion.