STIMULATION OF HETEROLOGOUS PROTEIN-DEGRADATION BY THE VPU PROTEIN OFHIV-1 REQUIRES THE TRANSMEMBRANE AND CYTOPLASMIC DOMAINS OF CD4

The small membrane protein Vpu of human immunodeficiency virus type 1 stimulates rapid degradation of CD4 molecules that are retained in the endoplasmic reticulum. To analyze the domain(s) of CD4 involved in Vp u-stimulated degradation, we examined degradation of hybrid proteins m ade between the vesicular stomatitis virus glycoprotein (VSV G) and CD 4. Vpu expression stimulated rapid degradation of a hybrid consisting of the extracellular domain of VSV G linked to the transmembrane and c ytoplasmic domains of CD4. Analysis of additional hybrids showed that both the cytoplasmic and transmembrane domains of CD4 were required fo r this Vpu-stimulated degradation. This conclusion is in apparent conf lict with a recent study showing that the cytoplasmic domain of CD4 al one is sufficient to cause Vpu-stimulated degradation of a CD8-CD4 hyb rid protein. The apparent conflict may be explained by the presence of related sequences or structures in the transmembrane domains of CD4 a nd CD8 that are involved in binding Vpu directly or that interact with the Vpu-stimulated degradation system. (C) 1994 Academic Press, inc.