Nef Proteins From Simian Immunodeficiency Viruses Are Tetherin Antagonists

Cell Host Microbe. 2009 Jul 23;6(1):54-67. doi: 10.1016/j.chom.2009.05.008. Epub 2009 Jun 4.


The tetherin/BST2/CD317 protein blocks the release of HIV-1 and other enveloped viruses by inducing tethering of nascent particles to infected cell surfaces. The HIV-1 Vpu protein antagonizes the antiviral activity of human but not monkey tetherins and many simian immunodeficiency viruses (SIVs) do not encode Vpu. Here, we show that the apparently "missing" antitetherin activity in SIVs has been acquired by several SIV Nef proteins. Specifically, SIV(MAC)/SIV(SMM), SIV(AGM), and SIV(BLU) Nef proteins can suppress tetherin activity. Notably, tetherin antagonism by SIV Nef proteins is species specific, is genetically separable from other Nef activities, and is most evident with simian rather than human tetherin proteins. Accordingly, a critical determinant of sensitivity to SIV(MAC) Nef in the tetherin cytoplasmic tail is variable in nonhuman primate tetherins and deleted in human tetherin, likely due to selective pressures imposed by viral antagonists, perhaps including Nef proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / immunology
  • Cell Line
  • GPI-Linked Proteins
  • Gene Products, nef / immunology*
  • Haplorhini
  • Humans
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / immunology*
  • Molecular Sequence Data
  • Simian Immunodeficiency Virus / growth & development
  • Simian Immunodeficiency Virus / immunology*


  • Antigens, CD
  • BST2 protein, human
  • GPI-Linked Proteins
  • Gene Products, nef
  • Membrane Glycoproteins