A problem that faces HIV is that its glycoprotein (gp160) is made in the endoplasmic reticulum at the same time as the CD4 antigen is being made. Since CD4 can bind to  gp160 under the conditions in the ER, it is likely that the proteins will complex and then will be targeted for destruction leading to the failure of virus production. To stop this happening, CD4 is degraded in the HIV-infected cell under the auspices of Vpu thereby allowing gp160 to pass along the secretion pathway from ER to Golgi to the plasma membrane. Vpu is a type 1, bitopic integral membrane protein of 81 amino acids. The C-terminal (cytoplasmic) region of the Vpu molecule interacts with alpha helices in the cytoplasmic region of CD4. There appears to be a direct correlation between the association of Vpu with the CD4 and its degradation. Regulation of the degree of degradation by Vpu is controlled by Vpu phosphorylation.  How the CD4 molecules are degraded is unclear but the use of inhibitors has suggested that the cytoplasmic proteasome may be involved. It should be noted, however, that some proteasomal inhibitors may not be truly specific. Vpu also reduces the expression of surface MHC class I proteins. This may be protective since it can stop recognition of infected cells by cytotoxic T lymphocytes. Vpu also stimulates virion release from the infected cell. Electron microscopy has shown that cells infected with Vpu mutants bind many more virus particles to their plasma membranes. The N terminal of the protein which is hydrophobic is involved in this and the process is not specific to HIV.

For further information see: Alan Frankel and John A. T. Young, HIV-1: Fifteen proteins and an RNA Annual Review of Biochemistry 67: 1-25, 1998