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.
The fusion of HIV-1 with CD4+ cells involves, in addition to CD4, specific cell surface molecules acting as fusion cofactors. Recently, we reported that the V3 loop of HIV-1 gp120 binds to GM3, a ganglioside abundantly expressed on CD4+ lymphocytes and macrophages. In the present study, we show that CD4 interacts with a reconstituted patch of GM3 by measuring the surface pressure with a Langmuir film balance. A biphasic increase in surface pressure is observed after the sequential addition of CD4 and gp120 under the GM3 monolayer, indicating the formation of the trimolecular complex GM3-CD4-gp120. Neutralization of gp120 with an anti-V3 antibody inhibits the secondary interaction with GM3, suggesting that the CD4-induced conformational change in gp120 allows the V3 loop to interact with GM3. In conclusion, this study supports the concept that glycolipids can function as HIV-1 fusion cofactors.
Hammache
D
D
Laboratoire de Biochimie et Biologie de la Nutrition, UPRESA-CNRS 6033, Faculté des Sciences de St. Jérôme, Marseille, France.
Yahi
N
N
Piéroni
G
G
Ariasi
F
F
Tamalet
C
C
Fantini
J
J
D000818:Animals; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D002240:Carbohydrate Sequence; D002417:Cattle; D004910:Erythrocyte Membrane / Q000378:metabolism; D005679:G(M3) Ganglioside / Q000737:chemistry / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008561:Membrane Fusion / Q000502:physiology; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011312:Pressure; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D013499:Surface Properties
D015704:CD4 Antigens; D005679:G(M3) Ganglioside; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D008563:Membrane Lipids; D010446:Peptide Fragments; D011994:Recombinant Proteins