STRUCTURAL MODULATIONS OF THE ENVELOPE GP120 GLYCOPROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 UPON OLIGOMERIZATION AND DIFFERENTIAL V3 LOOP EPITOPE EXPOSURE OF ISOLATES DISPLAYING DISTINCT TROPISM UPON VIRION-SOLUBLE RECEPTOR-BINDING

We investigated the binding of conformation-dependent anti-V2, anti-V3 , and anti-CD4-binding site monoclonal antibodies to monomeric and vir ion-associated gp120 from human immunodeficiency virus type 1 isolates displaying marked differences in cell tropism, For all viruses examin ed, we found that the half-maximal binding values of the anti-V2 and a nti-CD4-binding site antibodies with virion-associated gp120 were high er than those with monomeric gp120, but the maximum amount of antibodi es bound was diminished only for one of the anti-V2 antibodies tested. These observations suggest that upon gp120 oligomerization, the V2 lo op and CD4-binding site undergo conformational changes and that partic ular epitopes within these domains are occluded in the oligomeric gp12 0. In contrast, although the overall binding patterns and half-maximal binding values of the anti-V3 loop antibodies tested were similar wit h monomeric and oligomeric gp120, all the V3 loop epitopes examined we re less accessible to antibody binding on the virion surface. This mas king of the V3 loop is more pronounced for the primary-like macrophage -tropic isolates examined. Lastly, we observe that upon soluble recept or-virion binding, specific V3 loop epitopes that differ for viruses d isplaying different tropisms are exposed.