The V3 region of the envelope glycoprotein of human immunodeficiency virus type 1 binds sulfated polysaccharides and CD4-derived synthetic peptides.
gp120 is the envelope glycoprotein found on the surface of human immunodeficiency virus type 1 (HIV-1), and it binds to human cell surface CD4 receptors to initiate the HIV-1 infection process. It is now well-established that synthetic peptides from the V3 region on gp120 elicit antibodies that block HIV-1 infection and HIV-1-mediated cell fusion. Here we show that synthetic peptides derived from similar V3 regions of several isolates of HIV-1 bind [3H]heparin, and we also demonstrate that [3H]heparin binds to recombinant gp120 IIIB. The binding could be blocked by unlabeled heparin, dextran sulfate, and by a highly anionic benzylated synthetic peptide derived from human CD4 (amino acids 81-92). The nonbenzylated peptides from the same region were considerably less active. Unlabeled heparin, dextran sulfate, and the CD4-derived peptides were able to compete with the binding of soluble gp120 to immobilized antibodies against fragments of the V3 from isolate IIIB, but they had no effect on the binding of gp120 to anti-peptide antibodies targeted against another unrelated region of gp120. Biotin conjugated to the benzylated CD4-peptide bound to gp120 and was blocked from this binding by anti-V3 antibodies. These results indicate that the three materials that have been demonstrated by others to block HIV-1 infection in vitro, sulfated polysaccharides, certain CD4-derived synthetic peptides, and anti-V3 antibodies, may be acting through a common mechanism that includes binding to the V3 region of gp120 on HIV-1.
Batinić
D
D
Laboratory of Cellular Development and Oncology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Robey
F A
FA
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000517:prevention & control; D000595:Amino Acid Sequence; D015153:Blotting, Western; D015704:CD4 Antigens / Q000378:metabolism*; D016264:Dextran Sulfate / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D010455:Peptides; D011134:Polysaccharides; D011994:Recombinant Proteins; D006493:Heparin; D016264:Dextran Sulfate