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© The Rockefeller University Press,
0021-9525/2000//601 $5.00
The Journal of Cell Biology, Volume 150, Number 3,
, 2000 601-612
Original Article |
Rabies Virus-Induced Membrane Fusion Pathway
Fusion of rabies virus with membranes is triggered at low pH and is mediated by the viral glycoprotein (G). The rabies virus-induced fusion pathway was studied by investigating the effects of exogenous lipids having various dynamic molecular shapes on the fusion process. Inverted cone-shaped lysophosphatidylcholines (LPCs) blocked fusion at a stage subsequent to fusion peptide insertion into the target membrane. Consistent with the stalk-hypothesis, LPC with shorter alkyl chains inhibited fusion at lower membrane concentrations 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 the lag time preceding membrane merging, resulting in faster kinetics of fusion. This indicated that the rate limiting step for fusion is the formation of a fusion pore in a diaphragm of restricted hemifusion. The previously described cold-stabilized prefusion complex was also characterized. This intermediate is at a well-advanced stage of the fusion process when the hemifusion diaphragm is destabilized, but lipid mixing is still restricted, probably by a ring-like complex of glycoproteins. I provide evidence that this state has a dynamic character and that its lipid organization can reverse back to two lipid bilayers.
Key Words: rhabdovirus • prefusion complex • liposome • viral fusion glycoprotein • lysophosphatidylcholine
© 2000 The Rockefeller University Press
Abbreviations used in this paper: FIF, frozen intermediate of fusion; G, rabies virus glycoprotein; GPI-HA; HA ectodomain linked to glycosylphosphatidylinositol; HA, influenza virus hemagglutinin; LPC, lysophosphatidylcholine; NBD-PE, N-(7-nitro-2,1,3-benzoxadiazol-4-yl)-phosphatidylethanolamine; OA, oleic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; RHO-PE, N-(lissamine rhodamine B sulfonyl)-phosphatidylethanolamine; RVPC, rabies virus prefusion complex; TMRD-3000, tetramethylrhodamine dextran with a molecular mass of 3,000.
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