The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein

Cell Host Microbe. 2008 Apr 17;3(4):245-52. doi: 10.1016/j.chom.2008.03.001. Epub 2008 Mar 13.


The HIV-1 accessory protein Vpu counteracts a host factor that restricts virion release from infected cells. Here we show that the interferon-induced cellular protein BST-2/HM1.24/CD317 is such a factor. BST-2 is downregulated from the cell surface by Vpu, and BST-2 is specifically expressed in cells that support the vpu phenotype. Exogenous expression of BST-2 inhibits HIV-1 virion release, while suppression of BST-2 relieves the requirement for Vpu. Downregulation of BST-2 requires both the transmembrane/ion channel domain and conserved serines in the cytoplasmic domain of Vpu. Endogenous BST-2 colocalizes with the HIV-1 structural protein Gag in endosomes and at the plasma membrane, suggesting that BST-2 traps virions within and on infected cells. The unusual structure of BST-2, which includes a transmembrane domain and a lumenal GPI anchor, may allow it to retain nascent enveloped virions on cellular membranes, providing a mechanism of viral restriction counteracted by a specific viral accessory protein.

Publication types

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

MeSH terms

  • Antigens, CD / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Down-Regulation
  • Endosomes / metabolism
  • GPI-Linked Proteins
  • HIV Infections / metabolism*
  • HIV Infections / virology*
  • HIV-1 / physiology*
  • Human Immunodeficiency Virus Proteins / physiology*
  • Humans
  • Interferons / biosynthesis
  • Membrane Glycoproteins / metabolism*
  • Viral Regulatory and Accessory Proteins / physiology*
  • Virion / physiology*
  • Virus Replication
  • gag Gene Products, Human Immunodeficiency Virus / metabolism


  • Antigens, CD
  • BST2 protein, human
  • GPI-Linked Proteins
  • Human Immunodeficiency Virus Proteins
  • Membrane Glycoproteins
  • Viral Regulatory and Accessory Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • vpu protein, Human immunodeficiency virus 1
  • Interferons