Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins

Cell Rep. 2019 May 14;27(7):2092-2104.e10. doi: 10.1016/j.celrep.2019.04.063.


Guanylate-binding protein (GBP) 5 is an interferon (IFN)-inducible cellular factor reducing HIV-1 infectivity by an incompletely understood mechanism. Here, we show that this activity is shared by GBP2, but not by other members of the human GBP family. GBP2/5 decrease the activity of the cellular proprotein convertase furin, which mediates conversion of the HIV-1 envelope protein (Env) precursor gp160 into mature gp120 and gp41. Because this process primes HIV-1 Env for membrane fusion, viral particles produced in the presence of GBP2/5 are poorly infectious due to increased incorporation of non-functional gp160. Furin activity is critical for the processing of envelope glycoproteins of many viral pathogens. Consistently, GBP2/5 also inhibit Zika, measles, and influenza A virus replication and decrease infectivity of viral particles carrying glycoproteins of Marburg and murine leukemia viruses. Collectively, our results show that GPB2/5 exert broad antiviral activity by suppressing the activity of the virus-dependency factor furin.

Keywords: GBPs; HIV; Zika virus; furin; influenza A virus; measles virus; restriction factor; viral envelope proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Furin / genetics
  • Furin / metabolism*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • HEK293 Cells
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / metabolism*
  • HIV Envelope Protein gp41 / genetics
  • HIV Envelope Protein gp41 / metabolism*
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • Humans
  • Influenza A virus / genetics
  • Influenza A virus / metabolism
  • Measles virus / genetics
  • Measles virus / metabolism
  • Zika Virus / genetics
  • Zika Virus / metabolism


  • GBP5 protein, human
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • gp120 protein, Human immunodeficiency virus 1
  • gp41 protein, Human immunodeficiency virus 1
  • FURIN protein, human
  • Furin
  • GBP2 protein, human
  • GTP-Binding Proteins