title: Vpu is the main determinant for tetraspanin downregulation in HIV-1-infected cells.
abstract: Tetraspanins constitute a family of cellular proteins that organize various membrane-based processes. Several members of this family, including CD81, are actively recruited by HIV-1 Gag to viral assembly and release sites. Despite their enrichment at viral exit sites, the overall levels of tetraspanins are decreased in HIV-1-infected cells. Here, we identify Vpu as the main viral determinant for tetraspanin downregulation. We also show that reduction of CD81 levels by Vpu is not a by-product of CD4 or BST-2/tetherin elimination from the surfaces of infected cells and likely occurs through an interaction between Vpu and CD81. Finally, we document that Vpu-mediated downregulation of CD81 from the surfaces of infected T cells can contribute to preserving the infectiousness of viral particles, thus revealing a novel Vpu function that promotes virus propagation by modulating the host cell environment.
  
  
  OBJECTIVE
  The HIV-1 accessory protein Vpu has previously been shown to downregulate various host cell factors, thus helping the virus to overcome restriction barriers, evade immune attack, and maintain the infectivity of viral particles. Our study identifies tetraspanins as an additional group of host factors whose expression at the surfaces of infected cells is lowered by Vpu. While the downregulation of these integral membrane proteins, including CD81 and CD82, likely affects more than one function of HIV-1-infected cells, we document that Vpu-mediated lowering of CD81 levels in viral particles can be critical to maintaining their infectiousness.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Lambelé
authors.affiliation: Institute of Virology, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany.
authors.forename: Herwig
authors.initials: H
authors.lastname: Koppensteiner
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA Graduate Program in Cell and Molecular Biology, University of Vermont, Burlington, Vermont, USA.
authors.forename: Menelaos
authors.initials: M
authors.lastname: Symeonides
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA Graduate Program in Cell and Molecular Biology, University of Vermont, Burlington, Vermont, USA.
authors.forename: Nathan H
authors.initials: NH
authors.lastname: Roy
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA.
authors.forename: Jany
authors.initials: J
authors.lastname: Chan
authors.affiliation: Institute of Virology, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany Institute of Medical Virology and Epidemiology of Viral Diseases, University Clinic Tübingen, Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schindler
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA Graduate Program in Cell and Molecular Biology, University of Vermont, Burlington, Vermont, USA College of Medicine and CALS, University of Vermont, Burlington, Vermont, USA markus.thali@uvm.edu.
authors.forename: Markus
authors.initials: M
authors.lastname: Thali
mesh_terms: D015536:Down-Regulation; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D060225:Tetraspanin 28 / Q000235:genetics* / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D054298:Human Immunodeficiency Virus Proteins; D060225:Tetraspanin 28; D054334:Viral Regulatory and Accessory Proteins; C554798:CD81 protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins