Effect of lipid composition upon fusion of liposomes with Sendai virus membranes

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Abstract
How the lipid composition of liposomes determines their ability to fuse with Sendai virus membranes was tested. Liposomes were made of compositions designed to test postulated mechanisms of membrane fusion that require specific lipids. Fusion does not require the presence of lipids that can form micelles such as gangliosides or lipids that can undergo lamellar to hexagonal phase transitions such as phosphatidylethanolamine (PE), nor is a phosphatidylinositol (PI) to phosphatidic acid (PA) conversion required, since fusion occurs with liposomes containing phosphatidylcholine (PC) and any one of many different negatively charged lipids such as gangliosides, phosphatidylserine (PS), phosphatidylglycerol, dicetyl phosphate, PI or PA. A negatively charged lipid is required since fusion does not occur with neutral liposomes containing PC and a neutral lipid such as globoside, sphingomyelin or PE. Fusion of Sendai virus membranes with liposomes that contain PC and PS does not require Ca2+, so an anhydrous complex with Ca2+ or a Ca2+-induced lateral phase separation is not required although the possibility remains that viral binding causes a lateral phase separation. Sendai virus membranes can fuse with liposomes containing only PS, so a packing defect between domains of 2 different lipids is not required. The concentration of PS required for fusion to occur is .apprx. 10-fold higher than that required for ganglioside GD1a, which acts as a Sendai virus receptor. When cholesterol is added as a 3rd lipid to liposomes containing PC and GD1a, the amount of fusion decreses if the GD1a concentration is low. Cholesterol may decrease the availability of GD1a for multivalent binding. These data are consistent with the postulate that viral binding and the activities of the viral proteins play the major role in the fusion of viral and lipososmal membranes.

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