MEDIATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BINDING BY INTERACTION OF CELL-SURFACE HEPARAN-SULFATE PROTEOGLYCANS WITH THE V3 REGION OFENVELOPE GP120-GP41

The mechanism of heparan sulfate (HS)-mediated human immunodeficiency virus type 1 (HIV-1) binding to and infection of T cells was investiga ted 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 an alysis revealed that enzymatic removal of cell surface HS by heparitin ase 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 recombinan t 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 anti envelope or anti-CD4 antibodies from (SO42-)-S-35-labeled H9h cells th at had been incubated with soluble gp140. Soluble HS blocked the bindi ng of monoclonal antibodies that recognize the V3 and C4 domains of th e envelope protein to the surface of H9 cells chronically infected wit h HIV-1(IIIB). The V3 domain was shown to be the major site of envelop e-HS interaction by examining the effects of both antienvelope monoclo nal antibodies and heparitinase on the binding of soluble gp140 to H9h cells.