Inhibition of Human Immunodeficiency Virus Infection of CD4 + Cells by CD4-Free Glycopeptides from Monocytic U937 Cells

Abstract

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-α-mannose or methyl-α-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.