title: Anti-tetherin activities in Vpu-expressing primate lentiviruses.
abstract: BACKGROUND
  The anti-viral activity of the cellular restriction factor, BST-2/tetherin, was first observed as an ability to block the release of Vpu-minus HIV-1 from the surface of infected cells. However, tetherin restriction is also counteracted by primate lentiviruses that do not express a Vpu protein, where anti-tetherin functions are provided by either the Env protein (HIV-2, SIVtan) or the Nef protein (SIVsm/mac and SIVagm). Within the primate lentiviruses, Vpu is also present in the genomes of SIVcpz and certain SIVsyk viruses. We asked whether, in these viruses, anti-tetherin activity was always a property of Vpu, or if it had selectively evolved in HIV-1 to perform this function.
  
  
  RESULTS
  We found that despite the close relatedness of HIV-1 and SIVcpz, the chimpanzee viruses use Nef instead of Vpu to counteract tetherin. Furthermore, SIVcpz Nef proteins had activity against chimpanzee but not human tetherin. This specificity mapped to a short sequence that is present in the cytoplasmic tail of primate but not human tetherins, and this also accounts for the specificity of SIVsm/mac Nef for primate but not human tetherins. In contrast, Vpu proteins from four diverse members of the SIVsyk lineage all displayed an anti-tetherin activity that was active against macaque tetherin. Interestingly, Vpu from a SIVgsn isolate was also found to have activity against human tetherin.
  
  
  CONCLUSIONS
  Primate lentiviruses show a high degree of flexibility in their use of anti-tetherin factors, indicating a strong selective pressure to counteract tetherin restriction. The identification of an activity against human tetherin in SIVgsn Vpu suggests that the presence of Vpu in the ancestral SIVmus/mon/gsn virus believed to have contributed the 3' half of the HIV-1 genome may have played a role in the evolution of viruses that could counteract human tetherin and infect humans.
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Yang
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lopez
authors.forename: Heiko
authors.initials: H
authors.lastname: Hauser
authors.forename: Colin M
authors.initials: CM
authors.lastname: Exline
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Haworth
authors.forename: Paula M
authors.initials: PM
authors.lastname: Cannon
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins / Q000502:physiology*; D006801:Humans; D017958:Lentiviruses, Primate / Q000472:pathogenicity / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D002679:Pan troglodytes; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology*; D057074:Virus Release; D014779:Virus Replication; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D008562:Membrane Glycoproteins; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins