title: β-TrCP dependency of HIV-1 Vpu-induced downregulation of CD4 and BST-2/tetherin.
abstract: During evolution, pathogens have evolved strategies to counteract key cellular restriction mechanisms in order to efficiently invade target cells and fulfill essential steps of their replication cycle. Human Immunodeficiency Virus-1 and some Simian counterparts express a small multifunctional protein, Vpu, which influences viral replication. By acting as a multifunctional adapter, Vpu enhances viral particle release and infectivity. Therefore Vpu, an accessory protein, contributes to pathogenesis while avoiding superinfection. These effects rely mainly on the ability of Vpu to target the host proteins CD4 and BST-2/tetherin. Indeed, Vpu downregulates the cell surface expression of these receptors and subsequently induces their proteolysis via a mechanism involving a β -TrCP-containing E3 ubiquitin ligase complex. In this review, we will detail recent research aimed at elucidating the mechanism of Vpu-mediated CD4 and BST-2/tetherin downregulation and degradation as well as their subsequent consequences on viral pathogenesis.
authors.affiliation: Institute of Infection and Immunity, Department of Dermatology and Wound Healing, Cardiff University School of Medicine and University Hospital of Wales, Cardiff, Wales, UK.
authors.forename: Fabien P
authors.initials: FP
authors.lastname: Blanchet
authors.forename: J P
authors.initials: JP
authors.lastname: Mitchell
authors.forename: Vincent
authors.initials: V
authors.lastname: Piguet
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism*; D015536:Down-Regulation; D058851:GPI-Linked Proteins / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D021381:Protein Transport; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D014779:Virus Replication; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; D044844:beta-Transducin Repeat-Containing Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins