title: Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein.
abstract: Mammalian cells employ numerous innate cellular mechanisms to inhibit viral replication and spread. Tetherin, also known as Bst-2 or CD317, is a recently identified, IFN-induced, cellular response factor that blocks release of HIV-1 and other retroviruses from infected cells. The means by which tetherin retains retroviruses on the cell surface, as well as the mechanism used by the HIV-1 accessory protein Vpu to antagonize tetherin function and promote HIV-1 release, are unknown. Here, we document that tetherin functions as a broadly acting antiviral factor by demonstrating that both human and murine tetherin potently inhibit the release of the filovirus, Ebola, from the surface of cells. Expression of the Ebola glycoprotein (GP) antagonized the antiviral effect of human and murine tetherin and facilitated budding of Ebola particles, as did the HIV-1 Vpu protein. Conversely, Ebola GP could substitute for Vpu to promote HIV-1 virion release from tetherin-expressing cells, demonstrating a common cellular target for these divergent viral proteins. Ebola GP efficiently coimmunoprecipitated with tetherin, suggesting that the viral glycoprotein directly interferes with this host antiviral factor. These results demonstrate that tetherin is a cellular antiviral factor that restricts budding of structurally diverse enveloped viruses. Additionally, Ebola has evolved a highly effective strategy to combat this antiviral response elicited in the host during infection.
authors.affiliation: Department of Microbiology, School of Medicine, University of Pennsylvania, 225 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104-6076, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Kaletsky
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Francica
authors.forename: Caroline
authors.initials: C
authors.lastname: Agrawal-Gamse
authors.forename: Paul
authors.initials: P
authors.lastname: Bates
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D029043:Ebolavirus / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D016563:Filoviridae / Q000254:growth & development / Q000502:physiology*; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011485:Protein Binding; D014764:Viral Proteins / Q000378:metabolism / Q000502:physiology*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D014764:Viral Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2