title: Guanylate Binding Protein (GBP) 5 Is an Interferon-Inducible Inhibitor of HIV-1 Infectivity.
abstract: Guanylate binding proteins (GBPs) are an interferon (IFN)-inducible subfamily of guanosine triphosphatases (GTPases) with well-established activity against intracellular bacteria and parasites. Here we show that GBP5 potently restricts HIV-1 and other retroviruses. GBP5 is expressed in the primary target cells of HIV-1, where it impairs viral infectivity by interfering with the processing and virion incorporation of the viral envelope glycoprotein (Env). GBP5 levels in macrophages determine and inversely correlate with infectious HIV-1 yield over several orders of magnitude, which may explain the high donor variability in macrophage susceptibility to HIV. Antiviral activity requires Golgi localization of GBP5, but not its GTPase activity. Start codon mutations in the accessory vpu gene from macrophage-tropic HIV-1 strains conferred partial resistance to GBP5 inhibition by increasing Env expression. Our results identify GBP5 as an antiviral effector of the IFN response and may explain the increased frequency of defective vpu genes in primary HIV-1 strains.
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Krapp
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hotter
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Gawanbacht
authors.affiliation: National HIV and Retrovirology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3P6, Canada.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McLaren
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Silvia F
authors.initials: SF
authors.lastname: Kluge
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Stürzel
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Mack
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Reith
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Engelhart
authors.affiliation: Institute of Microbiology, University Hospital Center, University of Lausanne, 1015 Switzerland.
authors.forename: Angela
authors.initials: A
authors.lastname: Ciuffi
authors.affiliation: Gene Center and Department of Biochemistry, Ludwig-Maximilians-University Munich, 81377 Munich, Germany.
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sauter
authors.affiliation: J. Craig Venter Institute, Capricorn Ln, La Jolla, CA 92037, USA.
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany. Electronic address: frank.kirchhoff@uni-ulm.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
mesh_terms: D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006056:Golgi Apparatus / Q000201:enzymology / Q000235:genetics; D015658:HIV Infections / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D021381:Protein Transport; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism; D000086082:Viroporin Proteins
chemical_list: D019204:GTP-Binding Proteins; D054298:Human Immunodeficiency Virus Proteins; D007372:Interferons; D054334:Viral Regulatory and Accessory Proteins; C528873:GBP5 protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins