MEMBRANE ANCHORAGE OF GP160 IS NECESSARY AND SUFFICIENT TO PREVENT CD4 TRANSPORT TO THE CELL-SURFACE

The HIV envelope glycoprotein gp160 plays a major role in the posttran slational down-regulation of its receptor, CD4. In this report we have analyzed the requirements of both CD4 and gp160 involved in transport block of the gp160-CD4 complex causing the down-regulation of cell su rface CD4. Using a transient expression system we observed that both s oluble and membrane-bound CD4 were equally blocked by the wild-type gp 160, indicating that neither the transmembrane domain nor the cytoplas mic tail of CD4 affected its interaction with gp160 or exocytic transp ort block of the complex. Similarly, deletions of the gp160 cytoplasmi c domain or mutation in the transmembrane domain had little effect on its transport, or its ability to down-regulate CD4 surface expression. Furthermore, substitution of the gp160 transmembrane domain and cytop lasmic tail with that of the influenza virus hemagglutinin or with a g lycophosphatidylinositol moiety did not affect its ability to bind CD4 and block its transport However, soluble envelope glycoprotein constr ucts (either gp120 or soluble gp160) were unable to block CD4 transpor t to the cell surface despite their binding to CD4 within the ER. Take n together these results demonstrate that neither the gp160 cytoplasmi c tail nor the specific sequences of the transmembrane region of gp160 nor the membrane anchoring of CD4 were involved in ER retention of th e CD4-gp160 complex and that anchoring of gp160 to the ER membrane was responsible for gp160-mediated cell surface down-regulation of CD4. ( C) 1996 Academic Press, Inc.