Inhibition of human immunodeficiency virus infection of CD4+ cells by CD4-free glycopeptides from monocytic U937 cells.
We have previously demonstrated that human immunodeficiency virus (HIV) envelope glycoproteins have specific carbohydrate-binding properties for mannosyl/N-acetylglucosaminyl residues presented at high density on a carrier in vitro. Here, we investigated whether HIV envelope glycoprotein gp120 was able to interact with surface membrane carbohydrates of CD4+ cells by means of such lectin-carbohydrate interactions. CD4-free tryptic glycopeptides, prepared from the membrane of CD4+ monocytic U937 cells and partially purified by ConA-agarose affinity chromatography, could be eluted by mannan but not by methyl-alpha-mannose or methyl-alpha-glucose, which strongly suggests that they displayed oligomannosidic structures. These glycopeptides bound in a mannosyl-specific manner to radiolabeled recombinant gp120. Deglycosylation with N-glycanase which, as expected, strongly diminished binding of the glycopeptides to concanavalin A also abolished their interaction with gp120. In addition, the glycopeptides inhibited HIV infection of both U937 and CD4+ lymphoid CEM cells when preincubated with the virus. These findings indicate that, independently of the binding to CD4, mannosyl structures on CD4+ cells may play a role through lectin-carbohydrate interactions in envelope glycoprotein binding to a putative coreceptor(s) of HIV.
Mbemba
E
E
Faculté de Médecine Léonard de Vinci, Université Paris-Nord, Bobigny, France.
Carré
V
V
Atemezem
A
A
Saffar
L
L
Gluckman
J C
JC
Gattegno
L
L
D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D006020:Glycopeptides / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008351:Mannans / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology; D011994:Recombinant Proteins / Q000378:metabolism
D000998:Antiviral Agents; D006020:Glycopeptides; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D008351:Mannans; D011994:Recombinant Proteins