Guanylate Binding Protein (GBP) 5 Is an Interferon-Inducible Inhibitor of HIV-1 Infectivity

Cell Host Microbe. 2016 Apr 13;19(4):504-14. doi: 10.1016/j.chom.2016.02.019. Epub 2016 Mar 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / immunology*
  • Golgi Apparatus / enzymology
  • Golgi Apparatus / genetics
  • HIV Infections / enzymology*
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Human Immunodeficiency Virus Proteins / genetics
  • Human Immunodeficiency Virus Proteins / metabolism
  • Humans
  • Interferons / immunology*
  • Macrophages / immunology
  • Macrophages / virology
  • Protein Transport
  • Viral Regulatory and Accessory Proteins / genetics
  • Viral Regulatory and Accessory Proteins / metabolism


  • GBP5 protein, human
  • Human Immunodeficiency Virus Proteins
  • Viral Regulatory and Accessory Proteins
  • vpu protein, Human immunodeficiency virus 1
  • Interferons
  • GTP-Binding Proteins