Functional Interaction of Human Immunodeficiency Virus Type 1 Vpu and Gag with a Novel Member of the Tetratricopeptide Repeat Protein Family

Abstract

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.

Small glutamine-rich tetratricopeptide repeat-containing protein (SGT) interacts with the ubiquitin-dependent endocytosis (UbE) motif of the growth hormone receptor

“…Using GST fusion proteins encompassing the UbE motif, we pulled down a 35 kDa protein, identified by MS as small glutaminerich tetratricopeptide repeat (TPR)-containing protein (SGT). SGT, also known as viral protein U-binding protein (Ubp), was originally discovered as a protein interacting with envelope proteins of two viruses, namely parvovirus H-1 and HIV type 1 [25,26]. Sequence analysis of SGT revealed three tandem TPRs.…”

Translation Elongation Factor 1-Alpha Interacts Specifically with the Human Immunodeficiency Virus Type 1 Gag Polyprotein

“…HIV-1 Gag interacts with filamentous actin (69), and actin is found within HIV-1 virions (65). More recently, a member of the tetratricopeptide repeat family has been shown to associate with HIV-1 Gag and Vpu and may be involved in the Vpumediated enhancement of Gag particle release from the plasma membrane (12).…”

The viral protein U (Vpu)-interacting host protein ATP6V0C down-regulates cell-surface expression of tetherin and thereby contributes to HIV-1 release

“…To better understand Vpu function, and identify Vpu-interacting cellular proteins, we previously performed a yeast two-hybrid (Y2H) screen with HIV-1 Vpu as bait. We confirmed that small glutamine-rich tetratricopeptide repeat (TPR)-containing protein a (SGTA) is a Vpu-binding protein (47,48). Overexpression of SGTA impaired HIV-1 release independent of Vpu and tetherin expression (47)(48)(49)(50), whereas the depletion of SGTA had no significant effect on HIV-1 release or Vpu-mediated tetherin degradation (48).…”

“…We confirmed that small glutamine-rich tetratricopeptide repeat (TPR)-containing protein a (SGTA) is a Vpu-binding protein (47,48). Overexpression of SGTA impaired HIV-1 release independent of Vpu and tetherin expression (47)(48)(49)(50), whereas the depletion of SGTA had no significant effect on HIV-1 release or Vpu-mediated tetherin degradation (48). Further, we reported that overexpression of SGTA in the presence of Vpu induced a marked stabilization and cytosolic accumulation of the non-glycosylated form of tetherin.…”