Silencing of both beta-TrCP1 and HOS (beta-TrCP2) is required to suppress human immunodeficiency virus type 1 Vpu-mediated CD4 down-modulation

J Virol. 2007 Feb;81(3):1502-5. doi: 10.1128/JVI.01711-06. Epub 2006 Nov 22.

Abstract

The human immunodeficiency virus type 1 (HIV-1) Vpu protein interacts with CD4 within the endoplasmic reticula of infected cells and targets CD4 for degradation through interaction with beta-TrCP1. Mammals possess a homologue of beta-TrCP1, HOS, which is also named beta-TrCP2. We show by coimmunoprecipitation experiments that beta-TrCP2 binds Vpu and is able to induce CD4 down-modulation as efficiently as beta-TrCP1. In two different cell lines, HeLa CD4+ and Jurkat, Vpu-mediated CD4 down-modulation could not be reversed through the individual silencing of endogenous beta-TrCP1 or beta-TrCP2 but instead required the two genes to be silenced simultaneously.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4 Antigens / biosynthesis*
  • Down-Regulation
  • Gene Expression Regulation, Viral
  • Gene Silencing / physiology*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HeLa Cells
  • Human Immunodeficiency Virus Proteins
  • Humans
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Ubiquitin-Protein Ligases / deficiency
  • Ubiquitin-Protein Ligases / genetics*
  • Viral Regulatory and Accessory Proteins / physiology*
  • beta-Transducin Repeat-Containing Proteins / deficiency
  • beta-Transducin Repeat-Containing Proteins / genetics*

Substances

  • BTRC protein, human
  • CD4 Antigens
  • FBXW11 protein, human
  • Human Immunodeficiency Virus Proteins
  • Viral Regulatory and Accessory Proteins
  • beta-Transducin Repeat-Containing Proteins
  • vpu protein, Human immunodeficiency virus 1
  • Ubiquitin-Protein Ligases