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Tetherin antagonism by Vpu protects HIV-infected cells from antibody-dependent cell-mediated cytotoxicity
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Tetherin antagonism by Vpu protects HIV-infected cells from antibody-dependent cell-mediated cytotoxicity
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Journal Article
Tetherin antagonism by Vpu protects HIV-infected cells from antibody-dependent cell-mediated cytotoxicity
2014
Overview
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.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Antibody dependent cell cytotoxicity
/ Antibody-Dependent Cell Cytotoxicity - drug effects
/ Antibody-Dependent Cell Cytotoxicity - immunology
/ Cytoprotection - drug effects
/ GPI-Linked Proteins - antagonists & inhibitors
/ GPI-Linked Proteins - metabolism
/ HIV
/ HIV 1
/ Human immunodeficiency virus
/ Human immunodeficiency virus 1
/ Human Immunodeficiency Virus Proteins - metabolism
/ Humans
/ Interferon-alpha - pharmacology
/ Mutation
/ Receptors, Cell Surface - metabolism
/ RNA Interference - drug effects
/ Signaling Lymphocytic Activation Molecule Family Member 1
/ Viral Regulatory and Accessory Proteins - metabolism
/ Virions
/ Viruses
