Interaction of influenza virus with gangliosides and liposomes containing gangliosides.
It has already been shown that influenza virus binds unspecifically to liposomes containing ganglioside GM1 wheras with gangliosides GD1b and GT1b binding occurs in a specific and saturable manner [Slepushkin et al. (1986) Biol. Membr. 3, 229-235]. In the present study the mode of interaction between influenza virus and various gangliosides or phospholipid liposomes containing cholesterol and gangliosides has been investigated. The influence of exogenous gangliosides on the structure of the viral envelope was studied using fluorescent and photoactivatable phospholipids incorporated into the viral membrane. With both types of probes maximal effects of gangliosides were caused by GT1b. Addition of that ganglioside resulted in a marked decrease in the fluorescence polarization (P) of fluorescent labeled virus as well as in substantial changes in the binding of photoactivatable analogues of sphingomyelin and phosphatidylcholine to virus proteins, mainly hemagglutinin. The effects of GT1b and GD1b on P value were comparable, whereas gangliosides with other oligosaccharide chains caused much smaller changes in P. Furthermore GT1b but not GM1 influenced phospholipid-hemagglutinin cross-linking. Interaction of the virus with large unilamellar liposomes was monitored by two fluorescence assays based on resonance-energy transfer from the tryptophans and tyrosines of viral proteins to vesicles labeled with a triacylglycerol (anthrylvinyldioleoylglycerol) or from these labeled vesicles to virions labeled with a perylenoyl derivative of galactosylcerebroside (PGalSph). A third fluorescence assay was based on relief of self-quenching in PGalSph-labeled virions, upon low-pH-induced virus-liposome fusion. With all three fusion assays the changes of fluorescence caused by GT1b were more pronounced than those induced by GM1. On the other hand, virus-induced release of [14C]glucose from multilamellar liposomes was enhanced by GM1 but not by GT1b or GD1b. It is concluded that the interaction of GT1b or GD1b with virus hemagglutinin induces a rearrangement of the viral lipids rendering lipid bilayer areas of the viral envelope significantly fluid, which in turn promotes fusion of the virus with target membranes. Probably virus-liposome fusion and virus-induced liposome leakage are brought about by different mechanisms depending on specific or unspecific binding of the virions to the target.
Slepushkin
V A
VA
Ivanovsky Institute of Virology, Moscow USSR.
Starov
A I
AI
Bukrinskaya
A G
AG
Imbs
A B
AB
Martynova
M A
MA
Kogtev
L S
LS
Vodovozova
E L
EL
Timofeeva
N G
NG
Molotkovsky
J G
JG
Bergelson
L D
LD
D001665:Binding Sites; D004735:Energy Transfer; D005677:G(M1) Ganglioside / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D006386:Hemagglutination Tests; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000378:metabolism*; D009975:Orthomyxoviridae / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D005732:Gangliosides; D008081:Liposomes; C033851:ganglioside, GD1b; D005677:G(M1) Ganglioside; C016481:trisialoganglioside GT1