Stimulation of glycoprotein gp120 dissociation from the envelope glycoprotein complex of human immunodeficiency virus type 1 by soluble CD4 and CD4 peptide derivatives: implications for the role of the complementarity-determining region 3-like region in membrane fusion.
We have used a recombinant vaccinia virus vector encoding the envelope glycoprotein of human immunodeficiency virus type 1 to study receptor-induced structural changes related to membrane fusion. A truncated soluble form of human CD4 (sCD4) was found to stimulate dissociation of the external subunit (gp120) from the envelope glycoprotein complex of human immunodeficiency virus type 1 expressed at the cell surface. sCD4 stimulation of gp120 release was time- and concentration-dependent and was associated with specific binding of sCD4 to gp120. Synthetic peptide derivatives corresponding to residues 81-92 of human CD4 (overlapping the complementarity-determining region 3-like region) inhibited cell-cell fusion mediated by the interaction between recombinant vaccinia-encoded CD4 and human immunodeficiency virus envelope glycoprotein. These peptide derivatives also stimulated gp120 release from the envelope glycoprotein complex. An analogous peptide derivative from chimpanzee CD4 (containing a single Glu----Gly substitution at the position corresponding to CD4 residue 87) was considerably less active at inhibition of cell-cell fusion and stimulation of gp120 release, consistent with the known inhibitory effect of this substitution on the ability of membrane-associated CD4 to mediate cell fusion. These results suggest that the sCD4-induced release of gp120 reflects postbinding structural changes in the envelope glycoprotein complex involved in membrane fusion, with the complementarity-determining region 3-like region playing a critical role.
Berger
E A
EA
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Lifson
J D
JD
Eiden
L E
LE
D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008561:Membrane Fusion; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D014760:Viral Fusion Proteins / Q000378:metabolism
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D010455:Peptides; D011994:Recombinant Proteins; D014760:Viral Fusion Proteins