title: Determinants in HIV-2 Env and tetherin required for functional interaction.
abstract: BACKGROUND
  The interferon-inducible factor BST-2/tetherin blocks the release of nascent virions from the surface of infected cells for certain enveloped virus families. The primate lentiviruses have evolved several counteracting mechanisms which, in the case of HIV-2, is a function of its Env protein. We sought to further understand the features of the Env protein and tetherin that are important for this interaction, and to evaluate the selective pressure on HIV-2 to maintain such an activity.
  
  
  RESULTS
  By examining Env mutants with changes in the ectodomain of the protein (virus ROD14) or the cytoplasmic tail (substitution Y707A) that render the proteins unable to counteract tetherin, we determined that an interaction between Env and tetherin is important for this activity. Furthermore, this Env-tetherin interaction required an alanine face in the tetherin ectodomain, although insertion of this domain into an artificial tetherin-like protein was not sufficient to confer sensitivity to the HIV-2 Env. The replication of virus carrying the ROD14 substitutions was significantly slower than the matched wild-type virus, but it acquired second-site mutations during passaging in the cytoplasmic tail of Env which restored the ability of the protein to both bind to and counteract tetherin.
  
  
  CONCLUSIONS
  These results shed light on the interaction between HIV-2 and tetherin, suggesting a physical interaction that maps to the ectodomains of both proteins and indicating a strong selection pressure to maintain an anti-tetherin activity in the HIV-2 Env.
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 502, Los Angeles, CA, 90033, USA. colinexline@gmail.com.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Exline
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 502, Los Angeles, CA, 90033, USA. suyang@usc.edu.
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 502, Los Angeles, CA, 90033, USA. khaworth@fredhutch.org.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Haworth
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 502, Los Angeles, CA, 90033, USA. srinivas.rengarajan@gmail.com.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rengarajan
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 502, Los Angeles, CA, 90033, USA. lalopezphd@gmail.com.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lopez
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 502, Los Angeles, CA, 90033, USA. magali.droniou@stilla.fr.
authors.forename: Magali E
authors.initials: ME
authors.lastname: Droniou
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 502, Los Angeles, CA, 90033, USA. seclen@usc.edu.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Seclen
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 502, Los Angeles, CA, 90033, USA. pcannon@usc.edu.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Cannon
mesh_terms: D020816:Amino Acid Motifs; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D015498:HIV-2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D009154:Mutation; D054730:Protein Interaction Domains and Motifs; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism; D014771:Virion; D014779:Virus Replication; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054334:Viral Regulatory and Accessory Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2