Direct restriction of virus release and incorporation of the interferon-induced protein BST-2 into HIV-1 particles

PLoS Pathog. 2010 Mar 5;6(3):e1000701. doi: 10.1371/journal.ppat.1000701.


Investigation of the Vpu protein of HIV-1 recently uncovered a novel aspect of the mammalian innate response to enveloped viruses: retention of progeny virions on the surface of infected cells by the interferon-induced, transmembrane and GPI-anchored protein BST-2 (CD317; tetherin). BST-2 inhibits diverse families of enveloped viruses, but how it restricts viral release is unclear. Here, immuno-electron microscopic data indicate that BST-2 is positioned to directly retain nascent HIV virions on the plasma membrane of infected cells and is incorporated into virions. Virion-incorporation was confirmed by capture of infectivity using antibody to the ectodomain of BST-2. Consistent with a direct tethering mechanism, we confirmed that proteolysis releases restricted virions and further show that this removed the ectodomain of BST-2 from the cell surface. Unexpectedly, enzymatic cleavage of GPI anchors did not release restricted virions, weighing against models in which individual BST-2 molecules span the virion and host cell membranes. Although the exact molecular topology of restriction remains unsolved, we suggest that the incorporation of BST-2 into viral envelopes underlies its broad restrictive activity, whereas its relative exclusion from virions and sites of viral assembly by proteins such as HIV-1 Vpu may provide viral antagonism of restriction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies / pharmacology
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cell Membrane / virology
  • Dithiothreitol / pharmacology
  • Down-Regulation / immunology
  • GPI-Linked Proteins
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • HIV Infections / virology*
  • HIV-1 / growth & development*
  • HIV-1 / immunology*
  • HIV-1 / metabolism
  • HeLa Cells
  • Human Immunodeficiency Virus Proteins / metabolism
  • Humans
  • Immunoblotting
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Microscopy, Electron
  • Phosphoinositide Phospholipase C / metabolism
  • Transfection
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism
  • Viral Regulatory and Accessory Proteins / metabolism
  • Virion / growth & development
  • Virion / immunology
  • Virion / metabolism


  • Antibodies
  • Antigens, CD
  • BST2 protein, human
  • GPI-Linked Proteins
  • Human Immunodeficiency Virus Proteins
  • Membrane Glycoproteins
  • Viral Envelope Proteins
  • Viral Regulatory and Accessory Proteins
  • vpu protein, Human immunodeficiency virus 1
  • Phosphoinositide Phospholipase C
  • Dithiothreitol