title: Tetherin antagonism by Vpu protects HIV-infected cells from antibody-dependent cell-mediated cytotoxicity.
abstract: Tetherin is an IFN-inducible transmembrane protein that inhibits the detachment of enveloped viruses from infected cells. HIV-1 overcomes this restriction factor by expressing HIV-1 viral protein U (Vpu), which down-regulates and degrades tetherin. We report that mutations in Vpu that impair tetherin antagonism increase the susceptibility of HIV-infected cells to antibody-dependent cell-mediated cytotoxicity (ADCC), and conversely that RNAi knockdown of tetherin, but not other cellular proteins down-modulated by Vpu, decreases the susceptibility of HIV-infected cells to ADCC. These results reveal that Vpu protects HIV-infected cells from ADCC as a function of its ability to counteract tetherin. By serving as link between innate and adaptive immunity, the antiviral activity of tetherin may be augmented by virus-specific antibodies, and hence much greater than previously appreciated.
authors.affiliation: Department of Microbiology and Immunobiology, New England Primate Research Center, Harvard Medical School, Southborough, MA 01772.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Arias
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Heyer
authors.forename: Benjamin
authors.initials: B
authors.lastname: von Bredow
authors.forename: Kim L
authors.initials: KL
authors.lastname: Weisgrau
authors.forename: Brian
authors.initials: B
authors.lastname: Moldt
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Eva G
authors.initials: EG
authors.lastname: Rakasz
authors.forename: David T
authors.initials: DT
authors.lastname: Evans
mesh_terms: D019943:Amino Acid Substitution; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017353:Gene Deletion; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology*; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D034622:RNA Interference / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D054334:Viral Regulatory and Accessory 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; D016898:Interferon-alpha; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
keywords: AIDS; BST-2; CD317; lentivirus
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