A novel soluble analog of the HIV-1 fusion cofactor, globotriaosylceramide (Gb3), eliminates the cholesterol requirement for high affinity gp120/Gb3 interaction

We have analyzed the interaction of adamantyl Gb3 (adaGb3), a semi-synthetic soluble analog of Gb3, with HIV-1 surface envelope glycoprotein gp120. In this analog, which was orginally designed to inhibit verotoxin binding to its glycolipid receptor, Gb3, the fatty acid chain is replaced with a rigid globular hydrocarbon frame (adamantane). Despite its solubility, adaGb3 forms monolayers at an air-water interface. Compression isotherms of such monolayers demonstrated that the adamantane substitution resulted in a larger minimum molecular area and a more rigid, less compressible film than Gb3. Insertion of gp120 into adaGb3 monolayers was exponential whereas the gp120/Gb3 interaction curve was sigmoidal with a lag phase of 40 min. Adding cholesterol into authentic Gb3 monolayers abrogated the lag phase and increased the initial rate of interaction with gp120. This effect of cholesterol was not observed with phosphatidylcholine or sphingomyelin. In addition, verotoxin-bound adaGb3 or Gb3 plus cholesterol was recovered in fractions of comparable low density after ultracentrifugation through sucrose-density gradients in the presence of Triton X-100.The unique biological and physico-chemical properties of adaGb3 suggest that this analog may be a potent soluble mimic of Gb3, providing a novel concept for developing GSL-derived viral fusion inhibitors. We have analyzed the interaction of adamantyl Gb3 (adaGb3), a semi-synthetic soluble analog of Gb3, with HIV-1 surface envelope glycoprotein gp120. In this analog, which was orginally designed to inhibit verotoxin binding to its glycolipid receptor, Gb3, the fatty acid chain is replaced with a rigid globular hydrocarbon frame (adamantane). Despite its solubility, adaGb3 forms monolayers at an air-water interface. Compression isotherms of such monolayers demonstrated that the adamantane substitution resulted in a larger minimum molecular area and a more rigid, less compressible film than Gb3. Insertion of gp120 into adaGb3 monolayers was exponential whereas the gp120/Gb3 interaction curve was sigmoidal with a lag phase of 40 min. Adding cholesterol into authentic Gb3 monolayers abrogated the lag phase and increased the initial rate of interaction with gp120. This effect of cholesterol was not observed with phosphatidylcholine or sphingomyelin. In addition, verotoxin-bound adaGb3 or Gb3 plus cholesterol was recovered in fractions of comparable low density after ultracentrifugation through sucrose-density gradients in the presence of Triton X-100. The unique biological and physico-chemical properties of adaGb3 suggest that this analog may be a potent soluble mimic of Gb3, providing a novel concept for developing GSL-derived viral fusion inhibitors. The involvement of cellular glycosphingolipids (GSLs) in the attachment and fusion of enveloped viruses has been recognized for a long time (1Haywood A.M. Virus receptors: binding, adhesion strengthening, and changes in viral structure.J. Virol. 1994; 68: 1-5Google Scholar, 2Karlsson K.A. Microbial recognition of target-cell glycoconjugates.Curr. Opin. Struct. Biol. 1995; 5: 622-635Google Scholar). In the outer leaflet of the plasma membrane, GSLs can organize into moving platforms, or rafts, onto and into which specific proteins attach within the bilayer. Such rafts play an important role in endocytosis and signal transduction (3Brown R.E. Rose J. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface.Cell. 1992; 68: 533-544Google Scholar, 4Simons K. Ikonen E. Functional rafts in cell membranes.Nature. 1997; 387: 569-572Google Scholar, 5Brown R.E. Sphingolipid organization in biomembranes: what physical studies of model membranes reveal.J. Cell Sci. 1998; 111: 1-9Google Scholar). This lateral organization probably results from preferential packing of sphingolipids and cholesterol, based on their physico-chemical properties (6Thompson T.E. Tillack T.W. Organization of glycosphingolipids in bilayers and plasma membranes of mammalian cells.Annu. Rev. Biophys. Biophys. Chem. 1985; 14: 361-386Google Scholar, 7London E. Brown D.A. Insolubility of lipids in triton X-100: physical origin and relationship to sphingolipid/cholesterol membrane domains (rafts).Biochim. Biophys. Acta. 2000; 1508: 182-195Google Scholar). Consequently, sphingolipid-cholesterol rafts are insoluble in the detergent Triton X-100 at 4°C and those detergent-insoluble membranes can be purified by centrifugation on a sucrose-density gradient (3Brown R.E. Rose J. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface.Cell. 1992; 68: 533-544Google Scholar). In the present work, the term raft will be restricted to the sphingolipid/cholesterol-rich domains believed to exist in cell membranes prior to detergent treatment, since detergent-insoluble membranes and rafts are not necessarily identical (7London E. Brown D.A. Insolubility of lipids in triton X-100: physical origin and relationship to sphingolipid/cholesterol membrane domains (rafts).Biochim. Biophys. Acta. 2000; 1508: 182-195Google Scholar). Several lines of evidence support the concept that HIV-1 fusion occurs in GSLs-enriched microdomains of the plasma membrane: i) the CD4 receptor interacts with the monosialoganglioside GM3 and with globotriaosylceramide (Gb3), and is accordingly localized in GSL-enriched microdomains (8Sorice M. Parolini I. Sansolini T. Garofalo T. Dolo V. Sargiacomo M. Tai T. Peschle C. Torrisi M.R. Pavan A. Evidence for the existence of ganglioside-enriched plasma membrane domains in human peripheral lymphocytes.J. Lipid Res. 1997; 38: 969-980Google Scholar, 9Millan J. Cerny J. Horejsi V. Alonso M.A. CD4 segregates into specific detergent-resistant T-cell membrane microdomains.Tissue Antigens. 1999; 53: 33-40Google Scholar, 10Hammache D. Yahi N. Piéroni G. Ariasi F. Tamalet C. Fantini J. Sequential interaction of CD4 and HIV-1 gp120 with a reconstituted membrane patch of ganglioside GM3: implications for the role of glycolipids as potential HIV-1 fusion cofactors.Biochem. Biophys. Res. Commun. 1998; 246: 117-122Google Scholar, 11Hammache D. Yahi N. Maresca M. Piéroni G. Fantini J. Human erythrocyte glycosphingolipids as alternative cofactors for human immunodeficiency evidence for HIV-1 gp120 and reconstituted membrane microdomains of glycosphingolipids and Virol. 1999; the HIV-1 surface envelope glycoprotein gp120 to GM3 and Gb3 D. Yahi N. Piéroni G. Ariasi F. Tamalet C. Fantini J. Sequential interaction of CD4 and HIV-1 gp120 with a reconstituted membrane patch of ganglioside GM3: implications for the role of glycolipids as potential HIV-1 fusion cofactors.Biochem. Biophys. Res. Commun. 1998; 246: 117-122Google Scholar, 11Hammache D. Yahi N. Maresca M. Piéroni G. Fantini J. Human erythrocyte glycosphingolipids as alternative cofactors for human immunodeficiency evidence for HIV-1 gp120 and reconstituted membrane microdomains of glycosphingolipids and Virol. 1999; Scholar, J. N. F. of cell lines by human immunodeficiency is with cell surface of a potential alternative gp120 Sci. Scholar, D. Piéroni G. Yahi N. N. Tamalet C. Fantini J. interaction of HIV-1 and surface envelope with monolayers of and ganglioside Biol. Chem. 1998; the fusion is in GSLs-enriched microdomains G. C. J. E. C. raft microdomains lateral for HIV-1 2000; of cellular cholesterol and cell lines to and to by HIV-1 Lipid rafts and membrane cholesterol is for by Res. Scholar). GSLs are to the changes in the envelope glycoprotein for membrane fusion A. K. J. J. J. The globotriaosylceramide fusion by a envelope Sci. 1998; Scholar, T. A. of a of human immunodeficiency into cell lines Virol. 2000; Scholar). the of GSLs to HIV-1 Gb3 is the more potent D. Yahi N. Maresca M. Piéroni G. Fantini J. Human erythrocyte glycosphingolipids as alternative cofactors for human immunodeficiency evidence for HIV-1 gp120 and reconstituted membrane microdomains of glycosphingolipids and Virol. 1999; Scholar, A. K. J. J. J. The globotriaosylceramide fusion by a envelope Sci. 1998; Scholar, T. A. of a of human immunodeficiency into cell lines Virol. 2000; Scholar). studies have that of HIV-1 gp120 and inhibit HIV-1 fusion J. D. Yahi N. C. I. A. soluble of to the of HIV-1 gp120 and inhibit fusion and Biol. Chem. 1997; Scholar, C. D. J. C. A.M. Fantini J. of and and hydrocarbon and their Res. 2000; Scholar). studies and as a membrane a of with the 1997; Scholar, D. M. E. E. J. a specific binding on binding by and Scholar, G. Lipid of glycolipid receptor of for verotoxin binding in and J. 1994; have that the of the of and can the of the the and the of binding the may at the D. M. E. E. J. a specific binding on binding by and to is a for with a for viral J. D. Piéroni G. Yahi N. of microdomains in HIV-1 J. 2000; Scholar, J. soluble of glycolipids for studies of 2000; Scholar, to and Opin. Chem. Biol. 1998; Scholar, D. Fantini J. of glycolipid that binding of HIV-1 gp120 to Chem. 2000; Scholar). mimic the organization of in their membrane at the be soluble in the of is to binding developing soluble is a J. soluble of glycolipids for studies of 2000; Scholar). a of Gb3 was by the fatty acid chain of the with in a soluble semi-synthetic analog which for the verotoxin M. a soluble mimic which verotoxin binding to its glycolipid Biophys. Res. Commun. 1999; Scholar). to the interaction of with HIV-1 gp120. Gb3 was purified from human by as D. Yahi N. Maresca M. Piéroni G. Fantini J. Human erythrocyte glycosphingolipids as alternative cofactors for human immunodeficiency evidence for HIV-1 gp120 and reconstituted membrane microdomains of glycosphingolipids and Virol. 1999; Scholar). Gb3 purified from human was M. a soluble mimic which verotoxin binding to its glycolipid Biophys. Res. Commun. 1999; Scholar). was from purified Gb3 as M. a soluble mimic which verotoxin binding to its glycolipid Biophys. Res. Commun. 1999; Scholar). was by a D. M. E. M. The of can the substitution for Res. Scholar). The D. Fantini J. Yahi N. a of HIV-1 to cell surface was from The HIV-1 surface envelope glycoprotein gp120 was by the D. Piéroni G. Yahi N. N. Tamalet C. Fantini J. interaction of HIV-1 and surface envelope with monolayers of and ganglioside Biol. Chem. 1998; Scholar). phosphatidylcholine and from The surface was with a The the of isotherms and the of interaction of a with the film a of designed in a at of Gb3 or adaGb3 on of from as J. D. Piéroni G. Yahi N. of microdomains in HIV-1 J. 2000; Scholar). of the was for the interaction of HIV-1 or with glycolipid the was in the with a and for the The analyzed with the The of the was for surface of adaGb3 Gb3 or a of Gb3 and cholesterol in of Triton In replaced the The was at and in was and and to at for The was with of with or a of The was with of and of and by ultracentrifugation at for at The and glycolipid fractions from the gradient to with and glycolipids with analyzed with the the a sigmoidal curve was to the The molecular of Gb3 and its adamantyl adaGb3 are in The adamantane a rigid, isotherms of glycolipids are in glycolipids The of Gb3 and at film and the of in their isotherms that exist in the to film adaGb3 is soluble in to has the of Gb3 to a compressible film at the air-water interface. the for adaGb3 was than that observed for Gb3 This a to of adaGb3 Gb3, in the of a more rigid This is with the that the minimum molecular area for adaGb3 was larger than that of Gb3 molecular the surface for not Gb3, that adaGb3 in the This is not with D. M. E. M. The of can the substitution for Res. an adamantyl of that adamantane is not for this effect the adamantyl of not that the adamantane substitution specific physico-chemical in isotherms of Gb3 adaGb3 and The at a model for the organization of the adaGb3 as a of surface is in surface adaGb3 is to a minimum area of This is than the molecular of that be of an organization of the interface. of adaGb3 as the surface is increased and such may mimic the of Gb3 in cholesterol surface the and of adaGb3 to into the to the surface to that of of the to the will surface and surface surface a surface adaGb3 Gb3 and adaGb3 at the air-water at an initial surface of HIV-1 gp120 was in the The interaction of the viral glycoprotein with the glycolipid was by surface in the of gp120 into the film of Gb3 after an initial lag phase of 40 min. with of gp120 and Gb3 purified from of human lag phase the at an initial rate of and the was after of sigmoidal with the is In the of gp120 into the film of adaGb3 lag at an initial rate of In this the was after of with the viral The surface by gp120 was and for Gb3 and the of the of Gb3 and adaGb3 at initial and the surface by gp120 on was after the Gb3 and the of the film was as the initial of the The of the initial surface on the of the the of the interaction as for lipids and The surface of glycosphingolipids in biomembranes: a of molecular Biophys. Biol. 1994; Scholar). results with of Gb3 purified from human this was not the with the adamantyl of that to the with gp120 at surface in the of not This demonstrated that the adamantane was not for the specific interaction of the analog with gp120. Several lines of evidence suggest the involvement of the of gp120 in the recognition of plasma membrane In a from the to cell surface GSLs and inhibit HIV-1 fusion in cell D. Fantini J. Yahi N. a of HIV-1 to cell surface Scholar). in the of the into a film of Gb3 after a lag phase of min. The initial rate of was and the surface was observed after of sigmoidal with the is In the of the into a film of adaGb3 lag phase at an initial rate of The was after of The of interaction was by the with of Gb3 and adaGb3 at initial surface in the of the monolayers the initial increased demonstrated that the of the was of interaction a and Gb3 or The the surface after of the a film of Gb3 or adaGb3 at initial surface the of cholesterol, which is to glycolipids in their plasma membrane membrane (3Brown R.E. Rose J. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface.Cell. 1992; 68: 533-544Google Scholar, 4Simons K. Ikonen E. Functional rafts in cell membranes.Nature. 1997; 387: 569-572Google on this a of cholesterol and authentic Gb3 from was at the air-water interface. of the film at an initial of gp120 was in the The interaction at an initial rate of of lag phase The was after of for of cholesterol of Gb3 and that in this the initial rate was In gp120 to with a of Gb3 after 40 of as in The effect of cholesterol was for Gb3, since was not observed with or In the presence of cholesterol in a gp120 to the interaction of gp120 with a of and Gb3 the interaction after a lag phase of rate of The of cholesterol in the resulted in a of gp120 of the lag initial rate of and are in HIV-1 gp120 and Gb3 Gb3 at an initial surface of HIV-1 gp120 was in the the and the surface was as a of The initial rate of interaction and the surface with the of gp120. The results are the of in a at an initial surface of HIV-1 gp120 was in the the and the surface was as a of The initial rate of interaction and the surface with the of gp120. The results are the of is an important of membrane rafts K. Ikonen E. Functional rafts in cell membranes.Nature. 1997; 387: 569-572Google Scholar, 5Brown R.E. Sphingolipid organization in biomembranes: what physical studies of model membranes reveal.J. Cell Sci. 1998; 111: 1-9Google Scholar, 7London E. Brown D.A. Insolubility of lipids in triton X-100: physical origin and relationship to sphingolipid/cholesterol membrane domains (rafts).Biochim. Biophys. Acta. 2000; 1508: 182-195Google the effect of this on was in gp120 with monolayers with a lag phase of min. The rate of interaction after this initial phase was to the observed for Gb3 and the of interaction was observed gp120 was with a of Gb3 and not an of the interaction as with the effect of cholesterol was not observed Gb3 was in a of gp120 was with a In are present within microdomains and may to the binding of to monolayers in which the sphingolipids in the present not the interaction of gp120 with Gb3. the effect of cholesterol was observed Gb3 was in a of not was adaGb3 the lag phase and cholesterol for gp120/Gb3 adaGb3 was to Triton as insoluble or on a ultracentrifugation gradient after cell (7London E. Brown D.A. Insolubility of lipids in triton X-100: physical origin and relationship to sphingolipid/cholesterol membrane domains (rafts).Biochim. Biophys. Acta. 2000; 1508: 182-195Google Scholar). of such the lipids a of adaGb3 was in a to a low density are to (7London E. Brown D.A. Insolubility of lipids in triton X-100: physical origin and relationship to sphingolipid/cholesterol membrane domains (rafts).Biochim. Biophys. Acta. 2000; 1508: 182-195Google Scholar). In Gb3 not an the a was Gb3 was with cholesterol with the results of the was less than cholesterol to Gb3 to from the not be with In the presence of binding to the adaGb3 was The adaGb3 was of the Gb3 of the gradient for the the presence of Gb3 within the The Gb3 of this was on the cholesterol of increased the Gb3 binding was not increased suggest i) adaGb3 can detergent as Gb3 in the presence of cholesterol, for cholesterol, has effect in of binding, and molecular are recognized by and the potential of soluble of lipids is that may to in a of biological in presence of In to this monolayers of adaGb3 at the air-water and was in the in not the surface of the the was in the in presence of a of its interaction with adaGb3 was not not to adaGb3 and not the binding of adaGb3 to the is that a of and GSLs as binding on the cell surface of (1Haywood A.M. Virus receptors: binding, adhesion strengthening, and changes in viral structure.J. Virol. 1994; 68: 1-5Google Scholar, 2Karlsson K.A. Microbial recognition of target-cell glycoconjugates.Curr. Opin. Struct. Biol. 1995; 5: 622-635Google Scholar, 11Hammache D. Yahi N. Maresca M. Piéroni G. Fantini J. Human erythrocyte glycosphingolipids as alternative cofactors for human immunodeficiency evidence for HIV-1 gp120 and reconstituted membrane microdomains of glycosphingolipids and Virol. 1999; Scholar, J. D. Piéroni G. Yahi N. of microdomains in HIV-1 J. 2000; Scholar, for a to a Opin. Cell Biol. 1998; Scholar, for verotoxin and role in Biophys. Acta. 1999; Scholar, J. Maresca M. D. Yahi N. microdomains as attachment for and their on of signal transduction and of and J. 2000; Scholar). is a in developing of GSLs as specific of J. soluble of glycolipids for studies of 2000; Scholar, to and Opin. Chem. Biol. 1998; Scholar, D. Fantini J. of glycolipid that binding of HIV-1 gp120 to Chem. 2000; Scholar). The role by the in glycolipid has the of such which have in the mimic the and organization of GSLs in the plasma The of the of the and the membrane may play a role in the of the for binding, such that the may be receptor of glycolipid receptor J. Scholar). the for the of adamantyl of Gb3 M. a soluble mimic which verotoxin binding to its glycolipid Biophys. Res. Commun. 1999; the glycolipid receptor of the verotoxin for verotoxin and role in Biophys. Acta. 1999; Scholar). interaction is on the of Gb3 to present the for binding G. Lipid of glycolipid receptor of for verotoxin binding in and J. 1994; Scholar, A. receptor is by fatty acid and verotoxin fatty acid Biol. Chem. 1994; Scholar). was designed as an to mimic this effect in M. a soluble mimic which verotoxin binding to its glycolipid Biophys. Res. Commun. 1999; Scholar). In this of glycolipid the fatty acid chain is replaced by rigid hydrocarbon The adaGb3 analog a increased in with Gb3, and a in a binding as with the M. a soluble mimic which verotoxin binding to its glycolipid Biophys. Res. Commun. 1999; Scholar). Gb3 is by HIV-1 gp120 during the of the HIV-1 fusion the receptor A. K. J. J. J. The globotriaosylceramide fusion by a envelope Sci. 1998; Scholar, A. K. Rose of glycosphingolipids in HIV-1 of in 1999; and the is for gp120 binding M. of glycosphingolipids to their for acid as for gp120 Biol. Chem. 1999; was of to the interaction of gp120 with the film and a designed for that gp120 to adaGb3 more than to Gb3. The of was with of authentic Gb3 purified from human or human by of J. Fantini and C. A. and results In the of gp120 into a film of Gb3 a lag phase that to a binding of the is that the surface is increased the the in the lateral moving of lipids The surface of glycosphingolipids in biomembranes: a of molecular Biophys. Biol. 1994; Scholar). The of lag phase during the interaction gp120 and adaGb3 that the binding is which is in with the of verotoxin for adaGb3 with the Gb3 was that the adamantane packing in in the effect of the on receptor This the increased molecular area of the adaGb3 as with Gb3 The present results that adaGb3 at an Gb3 receptor for gp120 The increased surface at molecular is of and The lag time observed for gp120/Gb3 binding and the that the binding of gp120 to Gb3 and adaGb3 are the that Gb3 may have to a lateral to microdomains to gp120. the of such domains is low gp120 This is less for the the a lag phase for the initial rate of of gp120 is in the of adaGb3 with Gb3. results with a in with the involvement of the of gp120 in glycolipid recognition D. Piéroni G. Yahi N. N. Tamalet C. Fantini J. interaction of HIV-1 and surface envelope with monolayers of and ganglioside Biol. Chem. 1998; Scholar, D. Fantini J. Yahi N. a of HIV-1 to cell surface Scholar). that the of adaGb3 for verotoxin M. a soluble mimic which verotoxin binding to its glycolipid Biophys. Res. Commun. 1999; can be to HIV-1 gp120 and a adamantyl of glycolipids for glycolipid receptor In addition, that in adaGb3 a film at the air-water and that gp120 not in the of the This that the adaGb3 are to the of the film the of the the in the present is for the of adaGb3 binding to HIV-1 gp120. The properties of adaGb3 may such an for are not with that the adamantane frame not play a The that is by gp120 D. Piéroni G. Fantini J. as potential binding for in the plasma membrane in to the of membrane 1998; monolayers are not by gp120 a binding and membrane This was by the that the cellular increased binding fusion J. D. Piéroni G. Tamalet C. Fantini J. HIV-1 into 1998; 246: Scholar). The role of Gb3 in cell fusion A. K. J. J. J. The globotriaosylceramide fusion by a envelope Sci. 1998; the present as a model of this the the binding of to as in membranes A. rafts, and the of cholesterol in Sci. 2000; is with the that the of GSLs for binding can be by the receptor density within membrane microdomains or The of of adaGb3 at the air-water that the of the fatty acid chain with adamantane resulted in a more rigid with the increased of this Gb3 M. a soluble mimic which verotoxin binding to its glycolipid Biophys. Res. Commun. 1999; Scholar). This results in the of the surface that of at increased surface to the of the as in Despite a minimum molecular to the increased surface as the surface area was and This more rigid may mimic the organization of Gb3 in membrane rafts, as in a M. a soluble mimic which verotoxin binding to its glycolipid Biophys. Res. Commun. 1999; Scholar). may not the of may into rafts, which may in to its of a role in cell fusion J. D. Piéroni G. Tamalet C. Fantini J. HIV-1 into 1998; 246: Scholar). with this observed that cholesterol, which is to glycolipids in membrane rafts R.E. Sphingolipid organization in biomembranes: what physical studies of model membranes reveal.J. Cell Sci. 1998; 111: 1-9Google Scholar, A. rafts, and the of cholesterol in Sci. 2000; increased the initial rate of gp120 in a of authentic Gb3 and abrogated the lag this effect of cholesterol was for Gb3, since was not observed for or GSLs with a for HIV-1 gp120. The of effect of cholesterol on interaction may be by the low effect of cholesterol on monolayers Brown R.E. with 1994; Scholar). In the more chain of Gb3 may the of the in the the of cholesterol glycolipid This the and recognition of the glycolipid I. and recognition of the of glycolipids at the cell of the molecular J. Biol. in an for gp120. of cholesterol on receptor have been G. K. F. as of receptor 1997; Scholar). is that gp120 interacts with monolayers of and Gb3, with a lag phase of min. in this the gp120 are of Gb3, not are in with that the lag phase to a of the to an of the glycolipid for gp120 this as demonstrated by the and interaction observed gp120 and a film is that the cholesterol of the plasma membrane as to the a role in recognition during the in rafts, not to the of Gb3, since its presence in the not gp120 binding the Gb3 of the of the gradient with a interaction of rafts (7London E. Brown D.A. Insolubility of lipids in triton X-100: physical origin and relationship to sphingolipid/cholesterol membrane domains (rafts).Biochim. Biophys. Acta. 2000; 1508: 182-195Google binding was not increased which not be this larger interaction with cholesterol in biological and model 1999; may the Gb3 organization at the interface. In the Gb3 in the in the presence of cholesterol was increased by of binding was not that are not by The interaction of gp120 with of Gb3, and cholesterol was not by the presence of or in the reconstituted monolayers and effect on the Gb3 of cholesterol Triton on a suggest that cholesterol is for binding of gp120 to Gb3 This is in with the that the of within reconstituted membranes on the cholesterol A. rafts, and the of cholesterol in Sci. 2000; and that membrane cholesterol is for cellular by HIV-1 Lipid rafts and membrane cholesterol is for by Res. Scholar). are by the ultracentrifugation In Gb3 Triton X-100 with cholesterol, not In adaGb3 which the that this analog may mimic the organization of in detergent-insoluble In such the of the Gb3 to changes in the be for gp120 binding and to binding A. rafts, and the of cholesterol in Sci. 2000; Scholar). We that this effect is by important by the present is the of interaction Gb3 and HIV-1 gp120. gp120 interacts with and J. D. Piéroni G. Tamalet C. Fantini J. HIV-1 into 1998; 246: Scholar). the adamantyl of not monolayers at the air-water whereas which monolayers was not recognized by gp120 the adamantyl of for HIV-1 adaGb3 has unique physico-chemical and binding have been to inhibit HIV-1 in the of this ganglioside was to cell surface of CD4 M. A. A. A. CD4 and of HIV-1 by monosialoganglioside in Scholar). the interaction of gp120 with is with or Gb3 D. Yahi N. Maresca M. Piéroni G. Fantini J. Human erythrocyte glycosphingolipids as alternative cofactors for human immunodeficiency evidence for HIV-1 gp120 and reconstituted membrane microdomains of glycosphingolipids and Virol. 1999; Scholar). of or and human on CD4 through the of M. A. A. A. CD4 and of HIV-1 by monosialoganglioside in Scholar). the potential effect of on adaGb3 We that not to adaGb3 and not the interaction of the gp120 with In the results of the present that semi-synthetic of GSLs adaGb3 may mimic Gb3 providing a of molecular for the role of glycolipids and rafts in HIV-1 fusion D. of CD4 and into microdomains in a for membrane by human immunodeficiency Virol. Scholar, Human immunodeficiency CD4 and for into Virol. and biological for verotoxin and role in Biophys. Acta. 1999; Scholar). the of the evidence that can be in of cholesterol by a analog of a glycolipid a of by such glycolipid the of by N. Tamalet C. C. N. F. J. Fantini J. of the and in human immunodeficiency of 1999; Scholar, C. Yahi N. C. A.M. C. Fantini J. in the and of HIV-1 from and with 2000; and may a for HIV-1 in J. soluble of glycolipids for studies of 2000; Scholar). This was by of adamantyl Gb3

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