title: The sheep tetherin paralog oBST2B blocks envelope glycoprotein incorporation into nascent retroviral virions.
abstract: Bone marrow stromal cell antigen 2 (BST2) is a cellular restriction factor with a broad antiviral activity. In sheep, the BST2 gene is duplicated into two paralogs termed oBST2A and oBST2B. oBST2A impedes viral exit of the Jaagsiekte sheep retroviruses (JSRV), most probably by retaining virions at the cell membrane, similar to the "tethering" mechanism exerted by human BST2. In this study, we provide evidence that unlike oBST2A, oBST2B is limited to the Golgi apparatus and disrupts JSRV envelope (Env) trafficking by sequestering it. In turn, oBST2B leads to a reduction in Env incorporation into viral particles, which ultimately results in the release of virions that are less infectious. Furthermore, the activity of oBST2B does not seem to be restricted to retroviruses, as it also acts on vesicular stomatitis virus glycoproteins. Therefore, we suggest that oBST2B exerts antiviral activity using a mechanism distinct from the classical tethering restriction observed for oBST2A.
  
  
  OBJECTIVE
  BST2 is a powerful cellular restriction factor against a wide range of enveloped viruses. Sheep possess two paralogs of the BST2 gene called oBST2A and oBST2B. JSRV, the causative agent of a transmissible lung cancer of sheep, is known to be restricted by oBST2A. In this study, we show that unlike oBST2A, oBST2B impairs the normal cellular trafficking of JSRV envelope glycoproteins by sequestering them within the Golgi apparatus. We also show that oBST2B decreases the incorporation of envelope glycoprotein into JSRV viral particles, which in turn reduces virion infectivity. In conclusion, oBST2B exerts a novel antiviral activity that is distinct from those of BST2 proteins of other species.
authors.affiliation: Medical Research Council, University of Glasgow, Centre for Virus Research, Glasgow, Scotland.
authors.forename: Lita
authors.initials: L
authors.lastname: Murphy
authors.affiliation: Medical Research Council, University of Glasgow, Centre for Virus Research, Glasgow, Scotland.
authors.forename: Mariana
authors.initials: M
authors.lastname: Varela
authors.affiliation: UMR754, Université Claude Bernard Lyon 1, Institut National de la Recherche Agronomique, Ecole Pratique des Hautes Etudes, SFR BioSciences Gerland, Lyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Desloire
authors.affiliation: UMR754, Université Claude Bernard Lyon 1, Institut National de la Recherche Agronomique, Ecole Pratique des Hautes Etudes, SFR BioSciences Gerland, Lyon, France.
authors.forename: Najate
authors.initials: N
authors.lastname: Ftaich
authors.affiliation: Medical Research Council, University of Glasgow, Centre for Virus Research, Glasgow, Scotland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Murgia
authors.affiliation: Medical Research Council, University of Glasgow, Centre for Virus Research, Glasgow, Scotland.
authors.forename: Matthew
authors.initials: M
authors.lastname: Golder
authors.affiliation: Department of Infectious Diseases, King's College London School of Medicine, London, England.
authors.forename: Stuart
authors.initials: S
authors.lastname: Neil
authors.affiliation: Department of Animal Sciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Spencer
authors.affiliation: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Wootton
authors.affiliation: UMR5557 Microbial Ecology, Centre National de la Recherche Scientifique, Université Claude Bernard Lyon 1, Villeurbanne, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Lavillette
authors.affiliation: UMR754, Université Claude Bernard Lyon 1, Institut National de la Recherche Agronomique, Ecole Pratique des Hautes Etudes, SFR BioSciences Gerland, Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Terzian
authors.affiliation: Medical Research Council, University of Glasgow, Centre for Virus Research, Glasgow, Scotland.
authors.forename: Massimo
authors.initials: M
authors.lastname: Palmarini
authors.affiliation: UMR754, Université Claude Bernard Lyon 1, Institut National de la Recherche Agronomique, Ecole Pratique des Hautes Etudes, SFR BioSciences Gerland, Lyon, France frederick.arnaud@univ-lyon1.fr.
authors.forename: Frédérick
authors.initials: F
authors.lastname: Arnaud
mesh_terms: D000818:Animals; D006056:Golgi Apparatus / Q000378:metabolism; D022141:Jaagsiekte sheep retrovirus / Q000276:immunology* / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D021381:Protein Transport; D012756:Sheep; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors*; D014771:Virion / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins