Intracellular interaction of human immunodeficiency virus type 1 (ARV-2) envelope glycoprotein gp160 with CD4 blocks the movement and maturation of CD4 to the plasma membrane.
The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) plays a major role in the down-regulation of its receptor, CD4. Using a transient-expression system, we investigated the interaction of the HIV-1 envelope glycoprotein with CD4 during their movement through the intracellular membrane traffic. In singly transfected cells, the envelope glyprotein gp160 was synthesized, glycosylated, and localized predominantly in the endoplasmic reticulum. Only a minor fraction of gp160 was proteolytically cleaved, producing gp120 and gp41, and gp120 was secreted into the medium. On the other hand, the CD4 molecule, when expressed alone, was properly glycosylated and transported efficiently to the cell surface. However, when gp160 and CD4 were coexpressed in the same cell, the cell surface delivery of CD4 was greatly reduced. In coexpressing cells, CD4 formed a specific intracellular complex with gp160 as both proteins could be immunoprecipitated by antibodies against either the gp160 or CD4 (OKT4) but not by OKT4A, a blocking antibody against CD4. The specific gp160-CD4 complex was localized predominantly in the endoplasmic reticulum, and the CD4 in the complex did not acquire endoglycosidase H resistance. The present studies demonstrated that a specific intracellular interaction between gp160 and CD4 was responsible for the cell surface down-regulation of CD4 in cells expressing both the envelope glycoprotein of HIV-1 and its receptor, CD4.
Jabbar
M A
MA
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, School of Medicine 90024-1747.
Nayak
D P
DP
D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000276:immunology; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D015345:Oligonucleotide Probes; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D014162:Transfection
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015345:Oligonucleotide Probes