Emerging role of the host restriction factor tetherin in viral immune sensing

J Mol Biol. 2013 Dec 13;425(24):4956-64. doi: 10.1016/j.jmb.2013.09.029. Epub 2013 Sep 26.

Abstract

Tetherin (BST-2, CD317) is an interferon-inducible cellular factor that inhibits the release of diverse enveloped viruses by tethering them to the cell surface. Its importance in antiviral immunity is underscored by the observation that various viruses have evolved antagonists against this restriction factor. Accumulating evidence suggests that this is not only due to its ability to inhibit virus release but that tetherin also acts as an innate immune sensor of viral infections that activates NF-κB to induce an inflammatory response. Furthermore, tetherin modulates immune activation through interactions with the immunoglobulin-like transcript 7 (ILT7, LILRA4). This surface receptor is specifically expressed on plasmacytoid dendritic cells, which are the main producers of type I interferons in response to viral infections. Here, we summarize some of our current knowledge about the role of tetherin as a viral immune sensor and discuss how the accessory HIV-1 (human immunodeficiency virus type 1) Vpu protein counteracts this effect.

Keywords: DC; GPI; HIV-1; IFN; ILT7; IRF; PRR; SAMHD1; SIV; TAB; TAK1; TAK1-binding protein; TLR; TNF receptor-associated factor; TRAF; Toll-like receptor; Vpu; dendritic cell; glycosyl-phosphatidylinositol; human immunodeficiency virus type 1; immune signaling; immunoglobulin-like transcript 7; interferon; interferon regulatory factor; pDC; pattern-recognition receptor; plasmacytoid dendritic cell; simian immunodeficiency virus; sterile alpha motif and histidine/aspartic acid domain-containing protein 1; tetherin; transforming growth factor-β-activated kinase-1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Dendritic Cells / immunology
  • Dendritic Cells / virology
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation / immunology
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Human Immunodeficiency Virus Proteins / genetics
  • Human Immunodeficiency Virus Proteins / metabolism*
  • Humans
  • Immunity, Innate*
  • Models, Immunological
  • Molecular Sequence Data
  • NF-kappa B p50 Subunit / genetics
  • NF-kappa B p50 Subunit / metabolism*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Sequence Alignment
  • Viral Regulatory and Accessory Proteins / genetics
  • Viral Regulatory and Accessory Proteins / metabolism*
  • Virus Release

Substances

  • Antigens, CD
  • BST2 protein, human
  • GPI-Linked Proteins
  • Human Immunodeficiency Virus Proteins
  • LILRA4 protein, human
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • Receptors, Immunologic
  • Viral Regulatory and Accessory Proteins
  • vpu protein, Human immunodeficiency virus 1