Interactions of HIV-1 and HIV-2 envelope glycoproteins with sulphated polysaccharides and mannose-6-phosphate.
Envelope glycoproteins of human immunodeficiency viruses (HIV-1 and HIV-2) can interact with high-mannose glycans and with the mannosyl or N-acetylglucosaminyl core of complex-type oligosaccharidic structures. HIV-1 glycoproteins also specifically bind sulphated polysaccharides such as dextran sulphate (DS) and heparin. Here, we show that the latter property is shared by HIV-2 recombinant gp140 (rgp140) precursor glycoprotein. Binding of rgp140 and of corresponding rgp160 of HIV-1 to heparin- and DS-substituted (sulphated dextran beads; SDB) affinity matrices was inhibited by the soluble specific ligand and also by fetuin, asialofetuin or the anionic simple carbohydrate derivative mannose-6-phosphate (M6P). Interaction of HIV-1 rgp120 subunit with the two affinity matrices was also inhibited by M6P, but only rgp120 binding to heparin-agarose, and not that to SDB, was affected by fetuin and asialofetuin. These results suggest that HIV-1 and HIV-2 envelope glycoproteins presumably display different sulphated polysaccharide and carbohydrate recognition sites. Some of these may be common or in close proximity: with respect to rgp160, for example, the sites may be common on the gp41 moiety and/or in a region of gp120 which would be more accessible when expressed on rgp160 than on processed gp120, while they may be distinct on the cleaved gp120 subunit. Finally, because M6P is a marker of lysosomal enzymes, we verified that HIV-1 and HIV-2 envelope glycoproteins could specifically bind in a M6P-inhibitable manner to a representative lysosomal enzyme, bovine liver beta-glucuronidase coupled to agarose, suggesting that they may possibly interfere with lysosomal enzyme sorting in HIV-infected cells.
Mbemba
E
E
Laboratoire de Biologie Cellulaire, Faculté de Médecine Paris-Nord, Bobigny, France.
Gluckman
J C
JC
Gattegno
L
L
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D016264:Dextran Sulfate / Q000737:chemistry / Q000378:metabolism*; D015686:Gene Products, env / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D015498:HIV-2 / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008360:Mannosephosphates / Q000378:metabolism*; D011485:Protein Binding; D012685:Sepharose / Q000031:analogs & derivatives / Q000378:metabolism
D015686:Gene Products, env; D008360:Mannosephosphates; C037405:heparin-sepharose; C027693:mannose-6-phosphate; D006493:Heparin; D012685:Sepharose; D016264:Dextran Sulfate; D005966:Glucuronidase