Encyclopedia of AIDS

Living Edition
| Editors: Thomas J. Hope, Douglas Richman, Mario Stevenson

Nef/Env/Vpu/Tetherin

Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9610-6_377-1

Definition

The interferon-inducible protein tetherin (also called BST2, CD317, or HM1.24) is a key component of the innate immunity against retroviral infections. Tetherin was named after its unique ability to restrict the release of enveloped viruses by physically tethering them to the plasma membrane of infected cells. Notably, tetherin also acts as a pattern recognition receptor inducing NF-κB-dependent expression of antiviral genes upon sensing of budding virions.

At least three primate lentiviral proteins (Vpu, Nef, and Env) have evolved the ability to counteract tetherin and enable the virus to evade this restriction. Due to a constant evolutionary arms race between virus and host, antagonization of tetherin by viral proteins is frequently species-specific. Human tetherin, for example, is resistant against counteraction by many simian immunodeficiency viruses (SIV) and represents a significant hurdle for successful zoonotic transmissions of SIV to humans. Thus, the evolution of a...

Keywords

Codon Tyrosine Leukemia Cysteine Interferon 
This is a preview of subscription content, log in to check access

References

  1. Cocka LJ, Bates P. Identification of alternatively translated tetherin isoforms with differing antiviral and signaling activities. PLoS Pathog. 2012;8:e1002931. doi:10.1371/journal.ppat.1002931.PubMedCentralCrossRefPubMedGoogle Scholar
  2. Galão RP, Pickering S, Curnock R, Neil SJD. Retroviral retention activates a Syk-dependent HemITAM in human tetherin. Cell Host Microbe. 2014;16:291–303. doi:10.1016/j.chom.2014.08.005.PubMedCentralCrossRefPubMedGoogle Scholar
  3. Hotter D, Sauter D, Kirchhoff F. Emerging role of the host restriction factor tetherin in viral immune sensing. J Mol Biol. 2013;425:4956–64. doi:10.1016/j.jmb.2013.09.029.CrossRefPubMedGoogle Scholar
  4. Kluge SF, Mack K, Iyer SS, et al. Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin. Cell Host Microbe. 2014;16:639–50. doi:10.1016/j.chom.2014.10.002.PubMedCentralCrossRefPubMedGoogle Scholar
  5. Kupzig S, Korolchuk V, Rollason R, et al. Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic Cph Den. 2003;4:694–709.CrossRefGoogle Scholar
  6. Laplana M, Caruz A, Pineda JA, et al. Association of BST-2 gene variants with HIV disease progression underscores the role of BST-2 in HIV Type 1 infection. J Infect Dis. 2013;207:411–9. doi:10.1093/infdis/jis685.CrossRefPubMedGoogle Scholar
  7. Le Tortorec A, Neil SJD. Antagonism to and intracellular sequestration of human tetherin by the human immunodeficiency virus type 2 envelope glycoprotein. J Virol. 2009;83:11966–78. doi:10.1128/JVI. 01515-09.PubMedCentralCrossRefPubMedGoogle Scholar
  8. Matsuda A, Suzuki Y, Honda G, et al. Large-scale identification and characterization of human genes that activate NF-κB and MAPK signaling pathways. Oncogene. 2003;22:3307–18. doi:10.1038/sj.onc.1206406.CrossRefPubMedGoogle Scholar
  9. Neil SJD. The antiviral activities of tetherin. Curr Top Microbiol Immunol. 2013;371:67–104. doi:10.1007/978-3-642-37765-5_3.PubMedGoogle Scholar
  10. Neil SJD, Zang T, Bieniasz PD. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature. 2008;451:425–30. doi:10.1038/nature06553.CrossRefPubMedGoogle Scholar
  11. Perez-Caballero D, Zang T, Ebrahimi A, et al. Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell. 2009;139:499–511. doi:10.1016/j.cell.2009.08.039.PubMedCentralCrossRefPubMedGoogle Scholar
  12. Sauter D. Counteraction of the multifunctional restriction factor tetherin. Front Microbiol. 2014;5:163. doi:10.3389/fmicb.2014.00163.PubMedCentralCrossRefPubMedGoogle Scholar
  13. Sauter D, Schindler M, Specht A, et al. Tetherin-driven adaptation of Vpu and Nef function and the evolution of pandemic and nonpandemic HIV-1 strains. Cell Host Microbe. 2009;6:409–21. doi:10.1016/j.chom.2009.10.004.PubMedCentralCrossRefPubMedGoogle Scholar
  14. Sauter D, Specht A, Kirchhoff F. Tetherin: holding on and letting go. Cell. 2010;141:392–8. doi:10.1016/j.cell.2010.04.022.CrossRefPubMedGoogle Scholar
  15. Sauter D, Hotter D, Van Driessche B et al. Differential regulation of NF-κB-mediated proviral and antiviral host gene expression by primate lentiviral Nef and Vpu proteins. Cell Rep. 2015;10(4):586–99.Google Scholar
  16. Swiecki M, Omattage NS, Brett TJ. BST-2/tetherin: structural biology, viral antagonism, and immunobiology of a potent host antiviral factor. Mol Immunol. 2013;54:132–9. doi:10.1016/j.molimm.2012.11.008.CrossRefPubMedGoogle Scholar
  17. Tavano B, Galao RP, Graham DR, et al. Ig-like transcript 7, but not bone marrow stromal cell antigen 2 (also known as HM1.24, tetherin, or CD317), modulates plasmacytoid dendritic cell function in primary human blood leukocytes. J Immunol Baltim Md 1950. 2013;190:2622–30. doi:10.4049/jimmunol.1202391.Google Scholar
  18. Van Damme N, Goff D, Katsura C, et al. 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;3:245–52. doi:10.1016/j.chom.2008.03.001.PubMedCentralCrossRefPubMedGoogle Scholar
  19. Zhang F, Wilson SJ, Landford WC, et al. Nef proteins from simian immunodeficiency viruses are tetherin antagonists. Cell Host Microbe. 2009;6:54–67. doi:10.1016/j.chom.2009.05.008.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Institute of Molecular VirologyUlm University Medical CenterUlmGermany