Mediation of human immunodeficiency virus type 1 binding by interaction of cell surface heparan sulfate proteoglycans with the V3 region of envelope gp120-gp41.
The mechanism of heparan sulfate (HS)-mediated human immunodeficiency virus type 1 (HIV-1) binding to and infection of T cells was investigated with a clone (H9h) of the T-cell line H9 selected on the basis of its high level of cell surface CD4 expression. Semiquantitative PCR analysis revealed that enzymatic removal of cell surface HS by heparitinase resulted in a reduction of the amount of HIV-1 DNA present in H9h cells 4 h after exposure to virus. Assays of the binding of recombinant envelope proteins to H9h cells demonstrated a structural requirement for an oligomeric form of gp120/gp41 for HS-dependent binding to the cell surface. The ability of the HIV-1 envelope to bind simultaneously to HS and CD4 was shown by immunoprecipitation of HS with either antienvelope or anti-CD4 antibodies from 35SO4(2-)-labeled H9h cells that had been incubated with soluble gp140. Soluble HS blocked the binding of monoclonal antibodies that recognize the V3 and C4 domains of the envelope protein to the surface of H9 cells chronically infected with HIV-1IIIB. The V3 domain was shown to be the major site of envelope-HS interaction by examining the effects of both antienvelope monoclonal antibodies and heparitinase on the binding of soluble gp140 to H9h cells.
Roderiquez
G
G
Division of Hematologic Products, Food and Drug Administration, Bethesda, Maryland 20892.
Oravecz
T
T
Yanagishita
M
M
Bou-Habib
D C
DC
Mostowski
H
H
Norcross
M A
MA
D000911:Antibodies, Monoclonal; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008561:Membrane Fusion; D010446:Peptide Fragments / Q000378:metabolism*; D011133:Polysaccharide-Lyases / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D013601:T-Lymphocytes / Q000821:virology
D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D010446:Peptide Fragments; D011133:Polysaccharide-Lyases; D011509:Proteoglycans; C059762:HIV envelope protein gp120 (305-321); C021349:heparitinsulfate lyase