Functional interaction of human immunodeficiency virus type 1 Vpu and Gag with a novel member of the tetratricopeptide repeat protein family.
Viral protein U (Vpu) is a protein encoded by human immunodeficiency virus type 1 (HIV-1) that promotes the degradation of the virus receptor, CD4, and enhances the release of virus particles from cells. We isolated 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 human tissues at the RNA level. UBP is a novel member of the tetratricopeptide repeat (TPR) protein family containing four copies of the 34-amino-acid TPR motif. Other proteins that contain TPR motifs include members of the immunophilin superfamily, organelle-targeting proteins, and a protein phosphatase. UBP also interacts directly with HIV-1 Gag protein, 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-producing cells resulted in a significant reduction in HIV-1 virion release. Taken together, these data indicate that UBP plays a role in Vpu-mediated enhancement of particle release.
Callahan
M A
MA
McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
Handley
M A
MA
Lee
Y H
YH
Talbot
K J
KJ
Harper
J W
JW
Panganiban
A T
AT
D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016655:HIV Core Protein p24 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D011485:Protein Binding; D016415:Sequence Alignment; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D000086082:Viroporin Proteins
D002352:Carrier Proteins; D016655:HIV Core Protein p24; D054298:Human Immunodeficiency Virus Proteins; D018832:Molecular Chaperones; D054334:Viral Regulatory and Accessory Proteins; C114575:SGTA protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins