FUNCTIONAL INTERACTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VPU ANDGAG WITH A NOVEL MEMBER OF THE TETRATRICOPEPTIDE REPEAT PROTEIN FAMILY

Viral protein U (Vpu) is a protein encoded by human immunodeficiency v irus type 1 (HIV-1) that promotes the degradation of the virus recepto r, CD4, and enhances the release of virus particles from cells. We iso lated a cDNA that encodes a novel cellular protein that interacts with Vpu in vitro, in vivo, and in yeast cells. This Vpu-binding protein ( UBP) has a molecular mass of 41 kDa and is expressed ubiquitously in h uman tissues at the RNA level. UBP is a novel member of the tetratrico peptide repeat (TPR) protein family containing four copies of the 34-a mino-acid TPR motif. Other proteins that contain TPR motifs include me mbers of the immunophilin superfamily, organelle-targeting proteins, a nd a protein phosphatase. UBP also interacts directly with HN-I Gag pr otein, the principal structural component of the viral capsid, However , when Vpu and Gag are coexpressed, stable interaction between UBP and Gag is diminished. Furthermore, overexpression of UBP in virus-produc ing cells resulted in a significant reduction in HIV-1 virion release. Taken together, these data indicate that UBP plays a role in Vpu-medi ated enhancement of particle release.