title: Tetherin restricts direct cell-to-cell infection of HIV-1.
abstract: BACKGROUND
  Tetherin (BST-2/CD317/HM1.24) is an interferon (IFN)-inducible factor of the innate immune system, recently shown to exert antiviral activity against HIV-1 and other enveloped viruses by tethering nascent viral particles to the cell surface, thereby inhibiting viral release. In HIV-1 infection, the viral protein U (Vpu) counteracts this antiviral action by down-modulating tetherin from the cell surface. Viral dissemination between T-cells can occur via cell-free transmission or the more efficient direct cell-to-cell route through lipid raft-rich virological synapses, to which tetherin localizes.
  
  
  RESULTS
  We established a flow cytometry-based co-culture assay to distinguish viral transfer from viral transmission and investigated the influence of tetherin on cell-to-cell spread of HIV-1. Sup-T1 cells inducible for tetherin expression were used to examine the impact of effector and target cell tetherin expression on virus transfer and transmission. Using this assay, we showed that tetherin inhibits direct cell-to-cell virus transfer and transmission. Viral Vpu promoted viral transmission from tetherin-expressing cells by down-modulating tetherin from the effector cell surface. Further, we showed that tetherin on the target cell promotes viral transfer and transmission. Viral infectivity in itself was not affected by tetherin.
  
  
  CONCLUSIONS
  In addition to inhibiting viral release, tetherin also inhibits direct cell-to-cell spread. Viral protein Vpu counteracts this restriction, outweighing its possible cost of fitness in cell-to-cell transmission. The differential role of tetherin in effector and target cells suggest a role for tetherin in cell-cell contacts and virological synapses.
authors.affiliation: McGill University AIDS Center, Lady Davis Institute, Jewish General Hospital, Montréal, Canada.
authors.forename: Björn D
authors.initials: BD
authors.lastname: Kuhl
authors.forename: Richard D
authors.initials: RD
authors.lastname: Sloan
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Donahue
authors.forename: Tamara
authors.initials: T
authors.lastname: Bar-Magen
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism; D057074:Virus Release; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; 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