Conformational Changes in Cell Surface HIV-1 Envelope Glycoproteins Are Triggered by Cooperation between Cell Surface CD4 and Co-receptors*
- From the Section of Membrane Structure and Function, Laboratory of Experimental and Computational Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702
Abstract
We have continuously measured CD4-induced conformational changes of cell surface-expressed human immunodeficiency virus type-1 envelope glycoprotein gp120-gp41 in 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.
Footnotes
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↵* This work was supported by the AIDS Intramural Targeted Antiviral Program.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed: NCI-FCRDC, Bldg. 469, Rm. 213, P. O. Box B, Miller Dr., Frederick, MD 21702-1201. Tel.: 301-846-1446; Fax: 301-846-6192; E-mail: blumen{at}helix.nih.gov.
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↵1 The abbreviations used are: HIV, human immunodeficiency virus; M-tropic, macrophage-tropic; T-tropic, T cell-tropic; HA, hemagglutinin; FBS, fetal bovine serum; bis-ANS, 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid; DiI, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarboxycyanine perchlorate.
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↵2 P. L. St. J. Jones, unpublished observations.
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- Received June 9, 1997.
- Revision received October 2, 1997.
- The American Society for Biochemistry and Molecular Biology, Inc.
