Rabies virus-induced membrane fusion pathway

Fusion of rabies virus with membranes is triggered at low pH and is mediate d by the viral glycoprotein (G). The rabies virus-induced fusion pathway wa s studied by investigating the effects of exogenous lipids having various d ynamic molecular shapes on the fusion process. Inverted cone-shaped lysopho sphatidylcholines (LPCs) blocked fusion at a stage subsequent to fusion pep tide insertion into the target membrane. Consistent with the stalk-hypothes is, LPC with shorter alkyl chains inhibited fusion at lower membrane concen trations and this inhibition was compensated by the presence of oleic acid. However, under suboptimal fusion conditions, short chain LPCs, which were translocated in the inner leaflet of the membranes, considerably reduced th e lag time preceding membrane merging, resulting in faster kinetics of fusi on, This indicated that the rate limiting step for fusion is the formation of a fusion pore in a diaphragm of restricted hemifusion, The previously de scribed cold-stabilized prefusion complex was also characterized. This inte rmediate is at a well-advanced stage of the fusion process when the hemifus ion diaphragm is destabilized, but lipid mixing is still restricted, probab ly by a ringlike complex of glycoproteins. I provide evidence that this sta te has a dynamic character and that its lipid organization can reverse back to two lipid bilayers.