Conformational Changes in Cell Surface Hiv-1 Envelope Glycoproteins Are Triggered By Cooperation Between Cell Surface Cd4 and Co-Receptors

We have continuously measured CD4-induced conformational changes of cell surface expressed human immunodeficiency virus type-1 envelope glycoprotein gp120-gp41 irt situ using 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid, a fluorescent probe that binds to hydrophobic groups. CD4-expressing human T cell lines induced significant and rapid conformational changes (<1 min delay) in gp120-gp41 from T cell-tropic strains, and little conformational changes in gp120-gp41 from macrophage-tropic strains, with equivalent levels of envelope expression. Conversely, CD4-expressing human macrophages induced significant and rapid conformational changes in gp120-gp41 from macrophage-tropic strains, and little conformational changes in gp120-gp41 from T cell-tropic strains. Thus, the conformational changes undergone by gp120-gp41, which lead to membrane fusion, are highly cooperative and require both receptor and co-receptor. We used a dye transfer assay to show that neither membrane lipid fusion or fusion pore formation can occur with host cells having different tropism from the envelope. [References: 31]

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