Silencing of both beta-TrCP1 and HOS (beta-TrCP2) is required to suppress human immunodeficiency virus type 1 Vpu-mediated CD4 down-modulation.
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.
Butticaz
Christophe
C
Institute of Microbiology, University Hospital of Lausanne, Lausanne, Switzerland.
Michielin
Olivier
O
Wyniger
Josiane
J
Telenti
Amalio
A
Rothenberger
Sylvia
S
D015704:CD4 Antigens / Q000096:biosynthesis*; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology*; D044844:beta-Transducin Repeat-Containing Proteins / Q000172:deficiency / Q000235:genetics*; D000086082:Viroporin Proteins
D015704:CD4 Antigens; D054298:Human Immunodeficiency Virus Proteins; D044767:Ubiquitin-Protein Ligases; D054334:Viral Regulatory and Accessory Proteins; D044844:beta-Transducin Repeat-Containing Proteins; C471644:BTRC protein, human; C471645:FBXW11 protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins